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Webster, Donald Shaw. "Studies of carbamazepine metabolism." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/27680.
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The objective of this study was to examine aspects of carbamazepine metabolism, in order to contribute to a long term goal of a thorough examination of how the metabolism of carbamazepine is influenced by other drugs.
The first set of experiments were designed with the intent of determining values for the pharmacokinetic parameters of carbamazepine metabolism in male New Zealand white rabbits. Values were obtained for t[sub max] (60-90 min), t[sub ½](90-122 min), clearance (46.2-142.4 ml/min/kg), and the elimination constant (0.0057-0.0077 min⁻¹) in five test cases. In the remainder of cases, unexpected results were observed which did not allow calculation of these parameters. The plasma carbamazepine concentration was either delayed in reaching its peak concentration or it reached an apparent peak, but maintained that level for an extended period of time. It is thought that these differences between rabbits may have been due to differences in the rates of gastric emptying, a factor that may have been influenced by the food eaten by the animals in a period in excess of the 12 hours that some of the rabbits were fasted prior to the experiments. Alternatively, the time period of required sampling may have been underestimated. In addition, it is also possible that some degree of enterohepatic circulation is taking place. The relative positions of the curves for carbamazepine and for carbamazepine-10,11-epoxide suggest that there may be differences in the activities of hepatic monooxygenases and glucuronysyl transferases responsible for the metabolic fates of carbamazepine. The second set of experiments examined the influence of isoniazid and some of its principal metabolites on the conversion of carbamazepine to carbamazepine-10,11-epoxide in the S9 fraction of rat liver homogenate. This study is a prelude to planned in vivo studies of the interaction in rabbits. Three concentrations of each of isoniazid, acetyl hydrazine, acetylisoniazid, hydrazine, and isonicotinic acid were tested in a system containing constant concentrations of carbamazepine and of essential co-factors. The results indicated that there was a concentration dependent inhibition of carbamazepine metabolism by isoniazid, hydrazine, and isonicotinic acid. These types of experiments should expanded to include a range of carbamazepine concentrations so that an evaluation of the type of inhibition can be determined, as can be done Michaelis-Menton kinetics.Medicine, Faculty of
Anesthesiology, Pharmacology and Therapeutics, Department of
Graduate
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Amore, Benny Michael. "Mechanism of carbamazepine teratogenicity /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/7939.
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VASSEUR, ROSINE. "La carbamazepine : indications en psychiatrie." Clermont-Ferrand 1, 1988. http://www.theses.fr/1988CLF11039.
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Terra, Luciana Assis 1988. "Avaliação de transformação polimórfica em comprimidos do fármaco carbamazepina por espectroscopia de imagem no infravermelho próximo e ferramentas quimiométricas." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/249298.
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Orientador: Ronei Jesus PoppiDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química
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Resumo: A Espectroscopia de Imagem na região do Infravermelho Próximo juntamente com ferramentas quimiométricas foi utilizada para estudar a transformação polimórfica do fármaco carbamazepina (forma III para forma I) em formulações farmacêuticas do comprimido, geradas por aquecimento. Os mapas de distribuição de concentração das formas polimórficas I e III da carbamazepina no comprimido foram estimados por Mínimos Quadrados Parciais (PLS), Resolução Multivariada de Curvas (MCR) e Análise de Fatores Paralelos (PARAFAC), assim como o perfil de concentração em função do tempo durante o aquecimento, comparando os resultados obtidos quanto à eficácia na quantificação das formas polimórficas. Para o estudo da homogeneidade da distribuição do fármaco ao longo do comprimido, foram construídos histogramas. O trabalho está dividido em duas partes: na primeira parte foi realizado o mapeamento completo de um comprimido antes e após o aquecimento a 160 ºC, por 3 horas e os dados foram analisados por MCR. Na segunda parte do trabalho estudou-se a transformação polimórfica com o tempo a 140 ºC, em que foi realizado o mapeamento da parte central do comprimido, sendo nesse caso obtidas imagens a cada hora, com tempo total de 7 horas. Os resultados mostraram que os métodos PLS, MCR e PARAFAC foram capazes de obter informações sobre a transformação polimórfica, sendo MCR e PARAFAC capazes de estudar o processo dinâmico envolvido. Além disso, o MCR também foi capaz de fornecer os mapas de distribuição de concentrações em cada tempo de aquisição de dados, acompanhando a transformação polimórfica na superfície do comprimido
Abstract: The Near Infrared Chemical Imaging in conjunction with chemometric tools was used to study the polymorphic transformation of the drug carbamazepine (form III to form I) in pharmaceutical formulations tablets, generated by heating. The concentration distribution maps of the polymorphic forms I and III of carbamazepine in the tablet were estimated by Partial Least Squares (PLS), Multivariate Curve Resolution (MCR) and Parallel Factor Analysis (PARAFAC), as well as the concentration profile as a function of the heating time and the results were compared regarding the efficacy in quantification of the polymorphic forms. For the study of the homogeneity of distribution of the drug in the tablet, histograms were built. The work was divided into two parts: in the first part, it was conducted the mapping of the whole tablet before and after heating at 160 ºC for 3 hours and the data were analysed by MCR. In the second part, it was studied the polymorphic transformation over the time at 140 °C. Images of the central part of the tablet were obtained every hour during 7 hours. The results showed that the PLS, MCR and PARAFAC were able to obtain information about the polymorphic transformation and the MCR and PARAFAC were able to study the dynamic process involved as well. Furthermore, the MCR provided the concentration distribution map at each time of data acquisition, providing the polymorphic transformation on the tablet surface
Mestrado
Quimica Analitica
Mestra em Química
5
Marlot, Philippe. "In vitro evaluation of cytotoxicity caused by carbamazepine and its metabolites in association to carbamazepine-induced hypersensitivity reactions." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2025988/.
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Carbamazepine (CBZ), an anticonvulsant and mood-stabilising drug, is known to cause delayed type hypersensitivity reactions. These reactions occur only in a minority of patients treated with the drug, but often result in severe clinical outcomes. Although an association between CBZ-induced hypersensitivity reactions and HLA alleles has been demonstrated, the underlying mechanism(s) of toxicity are poorly understood. Cell death caused by CBZ and one of its metabolites, 9-acridinecarboxaldehyde (9-AC) was investigated. CBZ did not show cytotoxic effects in concentrations ranging from sub-therapeutic to supra-therapeutic. By contrast, 9-AC caused apoptosis in the lymphoblastoid cell line (50µM and 24 hours of exposure) and primary PBMCs (50 µM and 2 hours of exposure). PBMCs from 20 CBZ-naïve individuals showed significant inter-individual variability in the susceptibility to the cytotoxic effect of 9-AC. To further investigate the observed inter-individual variability, 331 immortalised lymphoblast cell lines of unrelated individuals from 4 populations were exposed to CBZ, CBZ-10,11 epoxide or 9-AC and cell viability was measured after 24 hour exposure. Considerable inter-individual variability in the cytotoxic response was observed for all three compounds. The genome wide association study (GWAS) revealed two genetic polymorphisms in dual oxidase 1 (DUOX1) and RP11-354|13.2 that were linked to cell toxicity at low concentrations of all three compounds. A SNP in DUOX1 was investigated further because of its biological plausibility. Genotyping of 153 patients did not show an association between this SNP and CBZ-induced hypersensitivity in Caucasians. Due to the higher than normal frequency of the DUOX1 variant in non-Caucasian patients (20%), the involvement of DUOX1 in the predisposition to CBZ-induced hypersensitivity reactions in non-Caucasians could not be excluded. To elucidate how T cell activation occurs in CBZ-induced hypersensitivity reactions, the protein binding capability of CBZ and two of its metabolites, CBZ-10,11 epoxide (CBZE) and 9-AC, to human serum albumin and glutathione S-transferase π was assessed. Only CBZE was found to bind covalently to these proteins. For 9-AC, no covalent products were observed but an indication of reversible binding was detected. Finally, newly developed genotyping methods for HLA-A*31:01 were investigated in comparison to sequence based typing. The methods were based on SSP-PCR. One of the methods showed exact accordance with the current gold standard but PCR failed to amplify the gene of interest and the control gene in considerable amount of samples (13.1%), while the second SSP-PCR typing method showed less reliability. In conclusion, the mechanisms of CBZ hypersensitivity has been investigated using a number of approaches designed to elucidate bioactivation of the drug, and how cytotoxicity links with genetic factors. The genomic approach may have the potential to identify novel biomarkers, but needs further studies with larger sample size.
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Alfirevic, Ana. "Molecular aspects of carbamazepine-induced hypersensitivity reactions." Thesis, University of Liverpool, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421067.
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Wurden, Colleen J. "Metabolism of carbamazepine and inhibitory drug interactions /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/7977.
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Martins, Armando Carvalho de Oliveira. "Processo oxidativo avançado UV/H2O2 na oxidação da carbamazepina : avaliação por ensaios respirometricos e ecotoxicologicos." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/257867.
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Orientador: Alexandre Nunes PoneziDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Civil, Arquitetura e Urbanismo
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Resumo: O efeito da poluição é resultado inerente da ocupação humana com grande impacto ao ambiente. Um problema atual é a contaminação dos corpos d'água com produtos de origem industrial, agrícola e produtos de origem farmacológica e de cuidado pessoal. Os fármacos são considerados contaminantes ambientais devido a estas moléculas serem biologicamente ativas. Neste trabalho foi estudada a biodegradabilidade direta da carbamazepina, sua degradação por processo oxidativo avançado e por processo oxidativo avançado seguido de respirometria. Foi utilizado como metodologia a cromatografia em camada delgada, cromatografia líquida de alta eficiência, análises toxicológicas, respirométricas, demanda química de oxigênio e carbono orgânico total. A avaliação do potencial de biodegradação direta da carbamazepina por microrganismos provenientes do lodo ativado e do solo não apresentaram resultados satisfatórios. A melhor concentração de carbamazepina a ser utilizada no processo oxidativo, foi de 10 ppm. As análises de carbono orgânico total, referente ao processo de oxidação em reator de ultravioleta com peróxido de hidrogênio, realizadas após o tratamento mostraram que a taxa de remoção de carbono da solução foi de 1%. A análise da demanda química de oxigênio, realizada a partir das amostras geradas do reator nos tempos de reação de 5, 15, 30, 45 e 60 minutos não apresentou qualquer mudança significativa. Os ensaios de respirometria (biodegradação) mostraram uma degradação de aproximadamente 1% do composto químico para todos os tratamentos com ultravioleta com peróxido de hidrogênio utilizados. Nos testes de biodegradabilidade os microrganismos não foram capazes de utilizar o fármaco como fonte de carbono e energia mesmo após o tratamento com ultravioleta com peróxido de hidrogênio. A avaliação do desenvolvimento dos microrganismos durante o ensaio de biodegradação apresenta decréscimo acentuado do número de microrganismos viáveis presentes tanto para o composto puro como também para os ensaios realizados após o tratamento com ultravioleta com peróxido de hidrogênio. Os subprodutos gerados no processo oxidativo avançado apresentam efeitos tóxicos agudos para a Ceriodaphinia dúbia e Vibrio fischeri nos ensaios toxicológicos.
Abstract: Pollution is a direct result of human occupation. Since the big human conglomerates appeared became clear its harmfulness to the environment. Today there is a growing concern with water pollution by industrial, agricultural, pharmaceutical and personal care products. Pharmaceutical and personal care products contaminates the water in the domestic effluent, or in an inappropriate disposal of then in urban trash. The pharmaceutical products are considered environmental contaminants because their molecules are biologically actives. In this study the direct biodegradability of carbamazepine, its degradation by advanced oxidation process and advanced oxidation process followed by respirometry were evaluated. The total organic carbon, chemical oxygen demand, thin layer chromatography, high pressure liquid chromatography and respirometry were utilized to obtain the results of this work. The biodegradability results by microorganisms in soil and silt were not satisfying. An optimal concentration of 10ppm of carbamazepina was used in the advanced oxidation process. The total organic carbon results of the advanced oxidation process in UV/H2O2 reactor after the treatment revealed a removal rate of 1%. The respirometry assays showed less than 1% degradation of the chemical compound for all UV/H2O2 treatment. The results indicate that the microorganisms were not able to use the pharmaceutical product as a carbon and energy source even after UV/H2O2 treatment. The evaluation of microscopic development during the biodegradation assays revealed a drastic fall in the number of viable microorganisms presents in the pure compound as well as after the advanced oxidation process. The toxicological assays showed that the advanced oxidation process generated sub products and have acute toxicological effects for Ceriodaphinia dúbia and Vibrio fischeri.
Mestrado
Saneamento e Ambiente
Mestre em Engenharia Civil
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Panesar, Sukhbinder Kaur. "The effect of carbamazepine on valproic acid metabolism." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26511.
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Modifications to the GCMS assay for valproic acid and 12 metabolites were attempted with respect to internal standards and derivatizing reagents. Four new internal standards, octanoic acid and 2-methylglutaric acid for analysis of VPA and metabolites and hexanoic acid and di-ռ-butylacetic acid for the analysis of hexadeuterated VPA and metabolites were used.
Two new derivatizing reagents, MSTFA and MTBSTFA, were tested as alternatives to the reagent previously used. TMS (MSTFA) and tBDMS derivatives were compared with respect to sensitivity, stability, and chromatographic time. The derivatives formed from MTBSTFA were extremely stable a major drawback was the formation of a diderivative of 3-keto VPA upon increased heating time and storage.
Preliminary data on the metabolism of D₆-VPA was obtained in one volunteer. The substitution of six deuterium atoms for six hydrogen atoms resulted in an isotope effect with decreased serum trough concentrations of 4-ene VPA and 2,4-diene VPA.
Valproic acid and carbamazepine are frequently coadministered in efforts to optimize seizure control. VPA is extensively metabolized while CBZ is known to induce the hepatic microsomal enzyme system, and thus, this is a potentially toxic interaction. Pharmacokinetic parameters for VPA were obtained before and after CBZ administration in five, healthy male volunteers. Increased plasma clearance of VPA accompanied by decreased plasma concentrations, serum half-life, and AUC values were observed after CBZ comedication. This was consistent with the ability of CBZ to induce the hepatic microsomal enzyme systems in a manner similar to phenobarbital.
Serum trough and steady state concentrations and AUC values for 12 metabolites were determined before and after CBZ administration. The AUC values for the monounsaturated
metabolites decreased after CBZ administration while the AUC values of the polar metabolites increased. The amount of 4-ene VPA, a potential hepatotoxin, was not increased in the serum after administration of CBZ. The amounts of the two diunsaturated metabolites, 2,3'-diene VPA and 2,4-diene VPA, were increased in the serum of the volunteers after CBZ administration. The amount of 2-ene trans VPA in the serum was significantly decreased after CBZ administration, while the amount of 3-keto VPA did not increase.
Urinary metabolic profiles were determined individually and grouped in pathways for the five volunteers before and after CBZ administration. Increased recoveries of 4-ene VPA, 4-keto VPA, and 2-PSA after CBZ administration were consistent with enhanced ω-1 oxidation.
Formation clearance, metabolic clearance, and fraction metabolized were determined for the metabolic pathways and for the individual metabolites. CBZ adminstration resulted in increased formation clearances for all pathways. The results obtained from this study indicate that CBZ caused a general induction of VPA metabolism and did not specifically affect a particular pathway. The effect of CBZ on the beta-oxidation pathway is not clearly understood. CBZ may cause a metabolic shift away from beta-oxidation, or actually inhibit beta-oxidation to some extent. As well, peroxisomal beta-oxidation may be involved.Pharmaceutical Sciences, Faculty of
Graduate
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Yip, V. L. M. "Carbamazepine hypersensitivity : linking metabolism to the immune response." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3002243/.
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Carbamazepine (CBZ) is an effective antiepileptic drug but has been associated with hypersensitivity reactions in up to 10% of patients. These reactions range from mild maculopapular exanthema to life-threatening conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The identification of CBZ-specific T cells and strong associations with specific human leukocyte antigen alleles provide evidence for immunological involvement. CBZ is extensively metabolised and forms several reactive metabolites. The aim of this thesis was to investigate the complex relationships between CBZ, its metabolism, the immune system, and genomics. Direct and microsomal incubations demonstrated that carbamazepine 10,11-epoxide (CBZE), the major metabolite of CBZ, formed a protein conjugate with human serum albumin (HSA) at His146. The same CBZE-modified HSA was also detected in patients tolerant of CBZ therapy. A second His146 CBZ-modified HSA adduct was identified in microsomal incubations, formed as a product of arene oxide providing the first chemical evidence that reactive metabolites of CBZ can modify soluble proteins. Healthy volunteers (n=8) and patients prescribed CBZ therapy (n=72) were recruited to investigate the influence of genetic variation on CBZ metabolism. Patient demographics and a mixture of rich and sparse pharmacokinetic (PK) samples were collected. Plasma levels of CBZ and four major metabolites were measured using a novel high performance liquid chromatography tandem mass spectrometric assay. There was significant variation in observed plasma concentrations of CBZ (14-fold) and its metabolites (approximately 30-fold). A population PK model was developed with nonlinear mixed effects modelling using the PK and clinical data collected from patients. Completion of autoinduction, total daily dosage and concomitant therapy with phenytoin were significant covariates that influenced the CBZ PK. Analysis of variance demonstrated that two single nucleotide polymorphisms (SNPs) in the gene ABCB1 and a single SNP in EPHX1 were significantly associated with altered plasma concentrations of CBZE. T cell clones (TCCs) were generated to CBZ and CBZE from two patients with a history of hypersensitivity to CBZ. All TCCs were CD4+ and secreted the cytokines IFN-γ, IL-13, granzyme B and perforin. TCC activation was MHC class II restricted and all TCCs were stimulated when CBZ was freshly added into the incubation mixture indicative of direct activation. A single TCC was activated when antigen presenting cells (APCs) were pulsed with CBZ indicative of a hapten mechanism. Transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from patients with a known history of CBZ hypersensitivity identified 9 CBZ/CBZE-specific mRNA and 39 CBZ/CBZE- miRNA transcripts. Pathway analysis mRNA and miRNA changes showed that antiviral response, psoriasis and inflammation were the most significant functions associated with exposure of cells from cases to CBZ and CBZE. In conclusion, these studies show that CBZ is transformed to stable and reactive metabolites, and these metabolites together with the parent drug, lead in susceptible individuals to an orchestrated response which involves transcriptional and immunological activation.
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OUDRHIRI, JAOUAD. "Lymphome centroblastique et carbamazepine : a propos d'un cas." Toulouse 3, 1990. http://www.theses.fr/1990TOU31034.
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Garnier, Jérôme. "Pneumopathie à la carbamazépine : A propos d'un cas et d'une revue de la littérature." Saint-Etienne, 1989. http://www.theses.fr/1989STET6006.
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Pinto, Mônia Aparecida Lemos. "Estudos termoanalíticos da carbamazepina: hidratação/desidratação, decomposição térmica e interações com excipientes empregados em formulações farmacêuticas." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/75/75135/tde-01112012-144158/.
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A carbamazepina (5H-dibenz[b, f]azepina-5-carboxamida) é um anticonvulsivante frequentemente utilizado no Brasil e em vários países. Ela apresenta quatro formas polimórficas e um di-hidratado, sendo ativa a Forma III. Entretanto, essa forma é altamente higroscópica podendo converter-se ao di-hidratado, menos ativo biologicamente. Nesse trabalho propõem-se avaliar o comportamento térmico da forma hidratada, visando à recuperação da forma ativa, por aquecimento. Para tanto, foi feito um estudo do comportamento térmico por TG/DTG-DTA e DSC em atmosfera dinâmica de ar e nitrogênio que evidenciou uma hidratação espontânea, não estequiométrica da Forma III, gerando um hidrato contendo 1,5 moléculas de água fracamente ligadas. Essa forma sofre desidratação seguida de fusão e conversão para a Forma I. Segue-se a decomposição em uma única etapa na qual ocorre liberação do ácido isociânico, conforme análise de gases desprendidos, por termogravimetria acoplada ao infravermelho (TG-FTIR). Estudos por calorimetria exploratória diferencial mostraram que a Forma III se funde e se cristaliza imediatamente, na Forma I, durante o aquecimento. A Forma I também se funde e ciclos de aquecimento/resfriamento posteriores evidenciaram que a substância se cristaliza apenas na Forma I por resfriamento. Estudos cinéticos da decomposição, em estado sólido, mostraram que não há alteração na substância pela eliminação da água por aquecimento, sendo determinados valores de energia de ativação da ordem de 98 ± 2 e 93 ± 2 kJ mol-1, respectivamente, para a amostra hidratada e submetida à secagem, assim como perfis semelhantes nas curvas de energia de ativação em função do fator de conversão. Estudos de interação fármaco-excipiente mostraram que há interação do fármaco hidratado com metilparabeno, hidroxipropilmetilcelulose (HPMC) e polivinilpirrolidona (PVP). Não se observou interação com o amido, celulose microcristalina, sílica coloidal, sacarina, carboximetilcelulose (CMC) e estearato de magnésio.Carbamazepine (5H-dibenz[b, f]azepina-5-carboxamida) is a anticonvulsivant frequently used in Brazil and many other countries. It presents four polymorphic forms and one di-hydrate, which is pharmacologically less active. In the present work a study of the possibility of recovering the hydrated form by heating is presented. Thus a thermal analytical investigation of the thermal behavior of the spontaneously hydrated carbamazepine sample was performed by TG/DTG-DTA and DSC in dynamic atmospheres of air and nitrogen, which evidenced the spontaneous hydration of the pharmaceutical leads to a non-stoichiometric Form III 1,5 hydrate. These water molecules seems to be weakly bonded to the solid. After dehydration the anhydrous form III converts to the Form I, that melts and decomposes in a single event, releasing isocyanic acid, according to the Evolved Gas Analysis, by thermogravimetry coupled to FTIR. Differential Scanning Calorimetry data reveled that the Form III melts and crystallizes in Form I, and subsequent cooling-heating cycles only present the Form I, during crystallization. Kinetic studies of solid state decomposition showed that there is any change in the substance by the water elimination by heating up to 120 °C. Activation energies of 98 ± 2 e 93 ± 2 kJ mol-1, respectively were found for the hydrated and heated samples, as well as similar activation energy vs. conversion factor profiles could be observed for these samples. Investigation on the drug-excipient interactions for the hydrated carbamazepine with methylparaben, hydroxypropylmethylcellulose (HPMC) and polyvinylpirrolidone (PVP), reveled interactions by changes in the polymorphic behavior of the pharmaceutical. Any interactions were noticed with starch, microcrystalline cellulose, colloidal silica, saccharine, carboxymethylcellulose (CMC) and magnesium stearate.
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Martins, Rodrigo Molina. "Desenvolvimento de dispersões sólidas microparticuladas contendo carbamazepina por spray congealing." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/60/60137/tde-17112010-112929/.
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O melhoramento das propriedades de dissolução de produtos farmacêuticos é extremamente importante, visto que houve um aumento de fármacos de baixa solubilidade disponibilizados no mercado farmacêutico nos últimos tempos. Várias técnicas têm sido utilizadas para melhorar as propriedades de dissolução destes fármacos como a cominuição, o uso de surfactantes e o preparo de dispersões sólidas. A preparação de dispersões sólidas é um método útil para dispersar moléculas de fármaco em uma matriz sólida hidrofílica. A técnica de spray congealing é usada para produção de micropartículas não necessitando de solventes orgânicos ou aquosos. O presente trabalho teve o objetivo de produzir micropartículas de dispersão sólida contendo carbamazepina (CBZ) preparadas por spray congealing e estudar a influência dos parâmetros do processo. A CBZ foi usada como fármaco modelo por apresentar baixa solubilidade e ser o medicamento de primeira escolha no tratamento da epilepsia psicomotora. Inicialmente foram preparadas dispersões sólidas usando como carreador o polioxilglicerídeo (Gelucire® 50/13), e os polietilenoglicóis (PEG 4000 e PEG 6000) nas proporções 1:9, 1:5 e 1:1 (fármaco:carreador), pelo método da fusão e posteriormente submetidas a estudos de solubilidade, onde a dispersão sólida com Gelucire® 50/13 (1:9) mostrou melhor solubilidade em relação a CBZ pura, sendo selecionada para o processo de produção de microparticulados por spray congealing. As micropartículas foram obtidas utilizando um planejamento experimental do tipo Box-Behnken, estudando os seguintes parâmetros: vazão de dispersão, vazão do ar de resfriamento e pressão de atomização num total de 15 experimentos. Os microparticulados foram caracterizados pelos estudos de tamanho de partícula, densidade aparente, densidade compactada, fator de Hausner, índice de Carr, ângulo de repouso, eficiência de encapsulação, atividade de água, solubilidade, teor de umidade e rendimento do processo, sendo todas estas propriedades avaliadas pela técnica de superfície de resposta (ANOVA). A análise estatística demonstrou que o rendimento sofreu influência das três variáveis enquanto que o teor de umidade foi dependente apenas da vazão de dispersão. As demais propriedades não sofreram influência significante dos parâmetros estudados. A dispersão sólida, a mistura física e as micropartículas de CBZ em Gelucire® 50/13 tiveram suas características físico-químicas avaliadas por difração de raios-x, espectroscopia em infravermelho, microscopia de plataforma a quente e análises térmicas (DSC e TG). Os resultados das análises mostraram que não ocorreram interações físico-químicas entre o fármaco e o carreador. No entanto, o processo de preparo da dispersão conduziu uma mudança no estado cristalino da CBZ convertendo parcialmente a forma polimórfica III para uma forma I. Os microparticulados apresentaram fluxo de bom a moderado com bons rendimentos (50-80 %), baixo teor de umidade (< 2%), atividade de água menor que 0,550 e boa eficiência de encapsulação (99,5 a 112 %). O tamanho médio das micropartículas variou de 53,09 a 78,75 µm.e sua morfologia analisada por microscopia eletrônica de varredura mostrou forma esférica, superfície lisa com algumas irregularidades e aparentemente não porosa. A solubilidade da CBZ contida nas micropartículas apresentou um aumento de 2,70 vezes em relação ao fármaco puro. As características do estado sólido das micropartículas foram semelhantes às da dispersão sólida. As micropartículas estudadas conduziram a um aumento na taxa de dissolução in vitro da CBZ comparada a sua respectiva dispersão sólida e a CBZ pura. Portanto, o spray congealing, é um método promissor para ser empregado e desenvolvido na fabricação de micropartículas de fármacos pouco solúveis.Improvement of dissolution properties of pharmaceutical products is extremely important, especially because the percentage of poor water soluble drugs has increased in the pharmaceutical market lately. Several techniques have been used to improve the dissolution properties of drugs such as grinding, the use of surfactants and preparation of solid dispersions. The preparation of solid dispersions is a useful method for disperse the drug molecules in a hydrophilic solid matrix. The spray congealing technique is used for production of microparticles and do not require organic or aqueous solvents. This work aimed to produce microparticles of solid dispersion prepared by spray congealing and to study the influence of process parameters. Carbamazepine (CBZ) was used as model drug due to its poor solubility and because it is the first choice drug for the treatment of psychomotor epilepsy. Initially solid dispersions were prepared using as carriers polyoxylglyceride (Gelucire® 50/13), and polyethylene glycols (PEG 4000 and PEG 6000) in the proportions 1:9, 1:5 and 1:1 (drug: carrier), applying the hot melt method .Solid dispersion with Gelucire ® 50/13 (1:9) showed better solubility compared to pure CBZ, being selected for the further production of microparticles by spray congealing. The microparticles were obtained using a Box Behnken experimental design, studying the following parameters: flow rate of liquid dispersion, flow rate of cooling air and atomizing pressure for a total of 15 experiments. The microparticles were characterized by studies of particle size, bulk density, compacted density, Hausner factor, Carr index, angle of repose, encapsulation efficiency, water activity, solubility, moisture content and yield of the process. These effects were analyzed by response surface technique (ANOVA). Statistical analysis showed that the yield was influenced by all three variables while the moisture was only dependent on the flow dispersion. The other properties were not significantly influenced by the parameters. The solid dispersion, physical mixture and microparticles of CBZ in Gelucire® 50/13 had their physical and chemical characteristics evaluated by x-ray diffraction, infrared spectroscopy, hot stage microscopy and thermal analysis (DSC and TG). The analysis of the results showed that there were no physical-chemical interactions between the drug and carrier. However, the preparation process of dispersion has led to a change in the crystalline state of CBZ, partially converting the polymorphic form III to the polymorphic form I. The microparticles showed good to moderate flow and good yields (50-80%), low moisture content (<2%), water activity lowerless than 0.550 and good encapsulation efficiency (99.5 to 112%) The average size microparticles ranged from 53.09 to 78.75 m. The morphology was analyzed by scanning electron microscopy and showed spherical shape, smooth surface with minor irregularities and apparently non-porous. The solubility of CBZ in the microparticles showed an increase of 2.70 times the solubility CBZ alone. The characteristics of microparticulated solid dispersions were similar to that of the solid dispersion. The microparticles studied led to an increase in dissolution rate of CBZ in vitro compared to its corresponding solid dispersion and pure CBZ. Therefore, the spray congealing is a promising method to be developed and employed in the manufacture of microparticles of poorly soluble drugs.
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Elliott, Emma-Claire. "Synthesis and structure-metabolism relationships of halogenated carbamazepine analogues." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569773.
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Adverse drug reactions are a significant burden on industry and healthcare providers. They account for approximately 5 % of hospital admissions and are a considerable cause of morbidity and mortality in patients. While it is widely considered that an individual's susceptibility to idiosyncratic reactions is caused by a variety of factors; ADRs are thought to be linked to the formation and accumulation of reactive drug metabolites rather than the parent drug. Of the patients administered carbamazepine 30-50 % are subject to the development of some form of adverse drug reaction. Carbamazepine is metabolized extensively in vivo and hypersensitivity reactions have been hypothetically linked to the formation of chemically reactive arene oxide or iminoquinone metabolites. In order to understand the mechanisms behind such ADRs it is important to synthesize a variety of chemical probes to observe changes in pharmacokinetic and pharmacodynamic properties of the compounds. The overall theme of this thesis is the synthesis and the examination of the structure-metabolism relationships for halogenated analogues of carbamazepine. It is divided into three main sections; a general introduction introduces the reader to the basics of drug metabolism from how drugs are metabolized to the implications of halogen substitution on the metabolism of drugs. It next covers the synthetic strategies employed in the formation of halogenated carbamazepine analogues before ending on a discussion of the key findings of the structure-metabolism relationships that may be derived from in vitro investigations
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NAVARRO, CATHERINE. "Effets cardiovasculaires de la carbamazepine : a propos d'un cas." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20136.
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Almeida, Ângela Augusta Soares de. "Presence of Carbamazepine in coastal systems : effects on bivalves." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13378.
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Mestrado em Toxicologia e EcotoxicologiaCarbamazepine (CBZ), an antiepileptic drug, is one of the most commonly detected pharmaceutical drugs in aquatic ecosystems, being used as a marker of anthropogenic pollution. Since CBZ is designed to exert a biological effect, when it reaches aquatic environment high probability exists for toxic effects on non-target organisms. In this way, the present study evaluated the acute (96 h) and chronic toxicity (28 d) of environmentally relevant concentrations of CBZ (0.00, 0.03, 0.30, 3.00, 9.00 μg/L) in the edible clams Venerupis decussata (a native species) and Venerupis philippinarum (an invasive species) collected from the Ria de Aveiro lagoon. The effects on both species were assessed through the use of a battery of biomarkers mainly related with health status and oxidative stress in the organisms. Furthermore, it was applied a promising alternative technique, the immunoassay ELISA for the direct CBZ quantification in clams’ tissues. The results obtained for the acute test showed that CBZ levels in clams’ tissues increased along the exposure concentration range, where V. decussata accumulated more CBZ (except for CBZ 9.00 μg/L) than V. philippinarum. After an exposure of 28 d V. decussata accumulated a higher concentration of CBZ with exception of the highest concentration of exposure, where the levels of CBZ accumulated were similar to the acute test. Although the clams accumulated lower levels of CBZ than the concentration of exposure, these concentrations were enough to impair the health status of the species under study and induce oxidative stress. A different response to CBZ was observed for both species exposed to the acute test. V. philippinarum increased the lipid peroxidation levels at the highest CBZ concentration, whereas V. decussata presented a significant decrease in this parameter. Glutathione S-transferase activity was stimulated for V. decussata and decreased for V. philippinarum. Nevertheless, after exposure to CBZ, for both species it was found an induction of glutathione reductase and superoxide dismutase. The results indicated that, probably, V. philippinarum have a deficient antioxidant defense system compared with V. decussata, being less capable to neutralize reactive oxygen species and thus appeared to be the most sensitive species to the CBZ effects. A 28 d exposure to CBZ resulted in a higher toxicity in V. decussata compared with the same species exposed to the acute test. This was mainly reflected by a lower activity/content in the mechanisms involved in the antioxidant defense system and thus, a lower capability to lead with oxidative stress induced by CBZ. The risk quotient determined for the Ria de Aveiro was higher than 1 indicating that an ecotoxicolgical risk is suspected. Furthermore, the bioaccumulation of CBZ in clams should be taken into consideration since it might be transferred along the food chain, ultimately affecting humans.
A carbamazepina (CBZ), uma droga antiepilética, é uma das drogas farmacêuticas frequentemente detetadas em ecossistemas aquáticos, sendo utilizada como um marcador da poluição antropogénica. Uma vez que a CBZ foi desenhada para exercer um efeito biológico, quando alcança o ambiente aquático existe uma elevada probabilidade para provocar efeitos tóxicos em organismos não-alvo. Desta forma, no presente estudo foi avaliada a toxicidade aguda (96 h) e crónica (28 d) de concentrações ambientalmente relevantes de CBZ (0.00, 0.03, 0.30, 3.00, 9.00 μg/L) em amêijoas comestíveis Venerupis decussata (nativa) e Venerupis philippinarum (invasora) capturadas na Ria de Aveiro. Os efeitos em ambas as espécies foram estudados utilizando uma bateria de biomarcadores principalmente relacionados com o estado de saúde e stress oxidativo nos organismos. Foi aplicada também uma técnica alternativa promissora, o imunoensaio ELISA para a quantificação direta de CBZ nos tecidos das amêijoas. Os resultados obtidos para o teste agudo mostraram um aumento da concentração de CBZ nos tecidos das amêijoas ao longo do intervalo de exposição, tendo V. decussata acumulado mais CBZ (exceto para CBZ 9.00 μg/L) do que V. philippinarum. Após uma exposição de 28 d a V. decussata acumulou uma concentração superior de CBZ, exceto na concentração mais elevada, onde os níveis concentrados foram similares aos do teste agudo. Apesar das amêijoas acumularem baixos níveis de CBZ comparando com a concentração de exposição, estes foram suficientes para comprometer o estado de saúde das espécies em estudo levando a uma condição de stress oxidativo. As duas espécies apresentaram uma resposta diferente à CBZ quando submetidas ao teste agudo. V. philippinarum aumentou os níveis de peroxidação lipídica na concentração mais alta de exposição, ao passo que V. decussata apresentou uma diminuição significativa deste parâmetro. A atividade da glutationa S-transferase foi estimulada no caso da V. decussata e diminuída para V. philippinarum. Não obstante, após a exposição a CBZ, em ambas as espécies ocorreu uma indução das atividades da glutationa reductase e superóxido dismutase. Os resultados indicaram que, provavelmente, V. philippinarum possui um sistema de defesa antioxidante deficiente quando comparada com V. decussata, sendo menos apta na neutralização das espécies reativas de oxigénio e portanto apresentou-se como a espécie mais sensível aos efeitos da CBZ. Uma exposição de 28 d à CBZ resultou numa toxicidade superior na espécie V. decussata por comparação com o teste agudo. Tal foi principalmente refletido na reduzida atividade/conteúdo nos mecanismos envolvidos no sistema de defesa antioxidante, traduzindo-se numa baixa capacidade para combater o stress oxidativo provocado pela CBZ. O quociente de risco determinado para a Ria de Aveiro foi superior a 1 indicando que se suspeita de um risco ecotoxicológico. A bioacumulação de CBZ pelas amêijoas torna evidente a possibilidade de ser transferida ao longo da cadeia alimentar, afetando em último caso o ser humano.
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Green, Victoria Jane. "The role of detoxication enzymes in adverse drug reactions." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283450.
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KEBIR, ABDEL-KARIM. "La carbamazepine dans les troubles bipolaires de l'humeur : efficacite, tolerance et role des taux plasmatiques." Toulouse 3, 1989. http://www.theses.fr/1989TOU31122.
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Kotcharaksa, Komgrit. "The Mechanisms, Products, and Kinetic of Carbamazepine-Free Chlorine Reactions." Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/36422.
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Carbamazepine (CBZ) is an antiepileptic drug widely detected in drinking water supplies and wastewater effluent. It has been previously found that CBZ is recalcitrant to biological removal processes. Therefore, active CBZ will be exposed to wastewater effluent disinfection processes, which for most treatment plants in the United States involves the addition of free chlorine. However, the chlorination mechanisms of CBZ have not been fully investigated and are currently poorly understood. Our experimental studies were conducted to examine the chlorination of CBZ under controlled conditions. The kinetics, products, and reactivity of CBZ/free chlorine reactions were investigated over the pH range of 5.5-10. Results show that free chlorine reacts with CBZ and the reactivity is pH dependent. Furthermore, the results indicate that temperature affects the reactivity of CBZ with free chlorine. The temperature experiment results were fitted with the Arrhenius equation. The calculated Ea and A values are 48.8 kJ/mol and 1.41x104 s-1, respectively. Four common intermediates were detected based on both UV and mass spectral analysis proposed structures were developed based on m/z from mass spectra.Master of Science
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Lichtenfels, Maike. "Investigation of immunogenetic risk factors for carbamazepine-induced hypersensitivity reactions." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/19333/.
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T-cell mediated hypersensitivity reactions (HSRs) to carbamazepine (CBZ), a commonly used anti-epileptic drug, occur only in a small proportion of patients, but can often be severe in nature. As the underlying pathomechanisms are not fully understood, it has proven difficult to predict who may be at risk of developing CBZ-induced HSRs. Recently, specific human leukocyte antigen (HLA) alleles have been identified as susceptibility factors for CBZ hypersensitivity in diverse populations, indicating that HLA molecules may be functionally involved in CBZ-induced T-cell activation. HLA-A*31:01 represents the latest example and has been implicated in CBZ-induced HSRs in Caucasian patients. Thus, the aim of this work was to explore the molecular interactions of CBZ with HLA-A*31:01 and drug-specific T-cells. The HLA restriction pattern of CBZ-reactive T-cells from a patient expressing HLA-A*31:01 was investigated. It was shown that CD8+ T-cells were activated in a HLA-A*31:01 dependent way. Further, HLA-DRB1*04:04 was found to be responsible for the stimulation of CD4+ T-cells, suggesting a common HLA haplotype may be involved in mediating T-cell responses to CBZ in Europeans. Next, in vitro priming of drug-naïve T-cells from HLA-A*31:01+ healthy volunteers against CBZ was attempted. Weak responses to CBZ could be detected in some but not all volunteers, indicating factors additional to HLA- A*31:01 are required to induce a primary stimulation of T-cells to CBZ. Besides, the removal of T-regulatory cells and use of dendritic cells as antigen- presenting cells seemed to generally improve priming conditions. In order to investigate whether CBZ affected the peptide-binding specificity of HLA-A*31:01, in silico and in vitro analysis were performed. In silico modelling provided a possible binding site for CBZ within the HLA peptide-binding cleft. A peptide elution study provided a preliminary indication that binding of CBZ to HLA-A*31:01 may alter the peptide repertoire presented by the allele, which could potentially result in T-cell activation. Most recently, it has been suggested that the T-cell receptor (TCR) may represent an additional predisposing factor for CBZ-induced HSRs. Accordingly, a protocol for the analysis of the TCR Vβ repertoire of drug-reactive T-cells by flow cytometry as well as CDR3 spectratyping was set up using T-cells from healthy donors primed against the model antigen SMX-NO. Both methods showed that antigen stimulation resulted in skewing of common TCR Vβ subtypes among the donors. Combined, the optimised methods will allow assessment of whether specific TCR clonotypes may be implicated in HLA- A*31:01 associated HSRs to CBZ. In summary, the data presented in this thesis provide initial evidence that CBZ is able to interact directly, through a non-covalent binding mechanism, with HLA-A*31:01 causing T-cell activation. However, it cannot be excluded that the stimulation of T-cells in vivo requires the formation of a hapten complex. Further work is needed to define other factors that are involved in predisposing an individual to CBZ hypersensitivity.
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García, Martínez Santos Noé. "Field and Laboratory Fish Tissue Accumulation of Carbamazepine and Amiodarone." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407838/.
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The goals of this dissertation work were to assess the bioaccumulation potential of carbamazepine and amiodarone, two widely used ionizable pharmaceutical compounds that possess mid-range and high LogD values, respectively, and to evaluate alternative methods to assess chemical accumulation in bluntnose minnows, catfish, and tilapia. Results indicated that carbamazepine does not appreciably bioaccumulate in fish tissue with BCFk and BAF carbamazepine values < 10. Amiodarone, however, with a log D of 5.87 at pH 7.4, accumulated in fish tissues with kinetic BCF values <2,400. Collectively, the data suggest that full and abbreviated laboratory-derived BCFs, BCFMs derived from S9 loss-of-parent assays, as well as field BAF values are similar for each of the two drugs. In summary, the results from this dissertation indicated: 1) The reduced design BCF test is a good estimate for the traditional OECD 305 test. 2) In vitro S9 metabolism assays provide comparable BCF estimates to the OECD 305 test. 3) Metabolism may play a large role in the accumulation of drugs in fish. 4) Reduced BCF tests and in vitro assays are cost effective and can reduce vertebrate testing.
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Rathman, Sara C. "Effects of oral carbamazepine administration on biotin metabolism in rats." [Gainesville, Fla.] : University of Florida, 2003. http://purl.fcla.edu/fcla/etd/UFE0001103.
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Kfuri, Camila Razuk. "Desenvolvimento de grânulos de carbamazepina por \'hot melt granulation\' em leito fluidizado." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/60/60137/tde-14102008-094131/.
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Os fármacos pertencentes às classes II e IV do sistema de classificação biofarmacêutica são aqueles sujeitos a problemas relacionados com a sua biodisponibilidade. Um dos procedimentos utilizados para melhorar a solubilidade de fármacos pouco solúveis é a granulação com materiais lipídicos ou cerosos. Para aumentar a solubilidade da carbamazepina, fármaco de classe II, ou seja, que apresenta baixa solubilidade e alta permeabilidade, inicialmente esta foi associada com os excipientes Gelucire® 50/13 ou Polietilenoglicol 6000, através de uma mistura física ou dispersão sólida. Estas associações foram submetidas a procedimentos analíticos como DSC, Infravermelho, Difração de Raios-X e teste de solubilidade em água. Nas misturas físicas a carbamazepina permaneceu estável, porém nas dispersões sólidas houve o aparecimento de polimorfismo. No entanto estes polimorfos também apresentam atividade terapêutica. As misturas físicas e as dispersões sólidas foram submetidas ao teste de solubilidade e as amostras que continham Gelucire® 50/13 aumentaram em torno de 15 vezes a solubilidade da carbamazepina em água, enquanto que as amostras que continham Polietilenoglicol 6000 aumentaram em torno de 14 vezes. Optou-se pela utilização do PEG 6000 devido à melhor compatibilidade deste com o equipamento utilizado. A granulação por Hot Melt em leito fluidizado foi realizada após alguns ensaios de fluidodinâmica utilizando a lactose spray dried como substrato. Durante os experimentos as condições do processo permaneceram estáveis e a curva característica foi típica de leito fluidizado. Os granulados foram obtidos utilizando o planejamento fatorial Box Behnken cujos fatores estudados foram: vazão de dispersão sólida, quantidade de dispersão sólida e pressão de atomização e em seguida caracterizados e avaliados. A maioria das propriedades físicas e farmacotécnicas dos granulados foi dependente da quantidade de dispersão sólida. A utilização do método de granulação por fusão em leito fluidizado melhorou o perfil de dissolução das cápsulas contendo os granulados, sendo que com o maior nível da quantidade de dispersão sólida houve um aumento significante na quantidade de carbamazepina liberada. Os resultados mostram que esta técnica é relevante para preparar dispersões sólidas com fármacos que apresentam baixa biodisponibilidade devido a sua baixa solubilidade.Drugs belonging to classes II and IV in the biopharmaceutical classification system are those having bioavailability problems. Granulation with waxy lipids is one of the procedures used to improve the solubility of poorly soluble drugs. To increase the solubility of carbamazepine a drug of class II that has low solubility but high permeability, its association with the excipients Gelucire® 50/13 or Polyethylene 6000, was done by physical mixtures or solid dispersions. The associations were subjected to analytical procedures such as Differential Scanning Calorimetry (DSC), infrared light, X-ray diffraction and tests of solubility in water. In physical mixtures carbamazepine remained stable, but showed different polymorphic forms in solid dispersions. However, the polymorphic forms were also therapeutically active.Solubility tests of physical mixtures and solid dispersions indicated that samples containing Gelucire ® 50 / 13 increased the solubility of carbamazepine in water about 15 times, while the ones containing Polyethylene glycol 6000 had an increase of about 14 times. PEG 6000 was the chosen carrier due to its better compatibility with the equipment used.Fluid dynamic tests using spray dried lactose as a substrate were preliminary to the granulation experiments in the fluidised bed. The process conditions remained stable during the experiments and the characteristic curve tracing was typical of fluidised beds. Granules were obtained in experiments that followed a Box Behnken factorial design, where the factors studied were: flow rate of the solid dispersion, amount of solid dispersion and atomization pressure .Most physical and technical granule properties were dependent on the quantity of solid dispersion. The method of granulation by hot melt in a fluidised bed improved the solubility profile of carbamazepine in granule containing capsules.Granules containing the highest amount of solid dispersion showed a significant increase in the amount of carbamazepine released. The results proved that this technique is relevant to the preparation of solid dispersions with low bioavailable drugs due to their poor solubility.
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Silva, Rita de Cassia da. "\"Preparação e aplicação de eletrodos de pasta de carbono modificados com ditiocarbamatos para análise de fármacos\"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/75/75132/tde-12042007-100734/.
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O morfolinoditiocarbamato (Mor); o piperidinoditiocarbamato (Pip) e o pirrolidinoditiocarbamato (Pyr) de rutênio derivados respectivamente da morfolina, piperidina e pirrolidina, três aminas alifáticas cíclicas foram preparados e caracterizados por análise elementar, espectroscopia vibracional na região do infravermelho, espectrometria de massa e análise térmica (termogravimetria TG e análise térmica diferencial DTA). A análise elementar mostrou que os compostos de fórmula geral Ru2DTC5.XH2O foram obtidos (DTC = Mor, Pip e Pyr e X = 4, 1,5 e 2 respectivamente); assim como a IV revelou que os complexos são monodentados, com duas bandas de absorção em torno de 1000 cm-1. A espectrometria de massas mostrou as estruturas moleculares e a estabilidade dos complexos, pois requerem alta energia de colisão para fragmentarem-se; alguns fragmentos puderam ser identificados. A análise térmica mostrou que após desidratação os DTC decompõem-se gerando sulfato e óxido de rutênio (III), dependendo da temperatura. Após caracterização, os complexos foram usados com modificadores na preparação de eletrodos de pasta de carbono modificados e seu desempenho avaliado por voltametria cíclica em diferentes meios e intervalos de potencial e em diferentes composições do material do eletrodo. Com base na melhor definição dos picos referentes aos processos anódicos e catódicos, assim como pela menor corrente residual, optou-se em usar como modificador o Ru2Pip5.1,5H2O, na proporção de 10% (m/m) na pasta. Eletrodos preparados com este modificador foram usados na determinação voltamétrica de carbamazepina (CBZ), usando CV. Na presença do analito a corrente do modificador aumenta proporcionalmente à concentração de CBZ no intervalo de 1,30 x 10-8 e 6,62 x 10-6 mol L-1, com limite de detecção de 3,18 x 10-7 mol L-1. O método foi aplicado na determinação de CBZ em urina sintética, usando procedimento de adição de padrão com recuperação da ordem de 97 104% e concordância com o método espectrofotométrico recomendado pela farmacopéia brasileira no intervalo de confiança de 95%.The morpholinedithiocarbamate (Mor); piperidinedithiocarbamate (Pip) and pirrolidinedithiocarbamate (Pyr), three cyclic amines derived respectivelly from morpholine, piperidine and pirrolidine complex of Ruthenium (III) were synthesized and characterized by elemental analysis, infra-red spectroscopy, mass spectrometry and thermal analysis (thermogravimetry TG and differential thermal analysis DTA). Elemental analysis showed that complexes of general formula Ru2DTC5.XH2O ((DTC = Mor, Pip e Pyr e X = 4, 1,5 e 2 respectively) were obtained. IR spectra revelead that the ligant behaves as a monodentate one with a duplet around 1000 cm-1. Mass spectrometry showed the molecular structures and the stability of the complexes, therefore they require high energy of collision to be broken up; some fragments could have been identified. Thermal analysis showed that after dehydration the complexes decomposed generating Ru2(SO4)3 and Ru2O3 as residues depending on the temperature, according to XDR analysis. After characterization the complexes were used as modifiers in the preparation of carbon paste electrodes. The performance of the modified electrodes (MCPE) was evaluated by cyclic voltammetry at different electrode composition and supporting electrolytes and potential intervals. On basis of peak definition and background current, the MCPERu2Pip5.1,5H2O, containing 10% of the complex, was chosen for further studies. The electrode was used in the determination of carbamazepine (CBZ) cyclic voltammetry. In the presence of CBZ the modifier current increased proportionally, to the analyte concentration in the 1,30 x 10-8 and 6,62 x 10-6 mol L-1. The method was applied in the determination of CBZ in synthetic urine sample spikes with the analyte with recoveries of 97 104%. Whem compared with a standart spectrophotometric procedure the results of the prposed method agreeded within 95% of confidence, according to the t-Student test.
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Santos, Helder Jacobina. "As Y-glutamil-transferase, transaminases e fosfatases alcalinas séricas em pacientes epilépticos tratados com carbamazepina." reponame:Repositório Institucional da FIOCRUZ, 2005. https://www.arca.fiocruz.br/handle/icict/5905.
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Helder Jacobina Santos As y-glutamil... 2005.pdf: 33243351 bytes, checksum: 707639696a2cd425ea90f9fb81248893 (MD5)Made available in DSpace on 2012-11-29T18:54:35Z (GMT). No. of bitstreams: 1 Helder Jacobina Santos As y-glutamil... 2005.pdf: 33243351 bytes, checksum: 707639696a2cd425ea90f9fb81248893 (MD5) Previous issue date: 2005
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil
A carbamazepina é a droga de eleição usada no tratamento de pacientes com epilepsia secundariamente generalizada. Além disso, a carbamazepina tem sido implicada no aumento sérico de algumas enzimas. Alguns autores encontraram prevalência de 13% e os outros, 22% e até 53% de alterações para as fosfatases alcalinas. Objetivo; As metas deste trabalho são determinar a proporção de alterações amostrais nas atividades das gama-glutamil transferase (GGT), fosfatases alcalinas totais (FA), transaminases (AST e ALT) e as concentrações séricas da carbamazepina em pacientes de ambulatórios de epilepsia. Metodologia: 0 desenho do estudo é descritivo, aprovado pelo Comitê de Ética local, no qual uma amostra de conveniência de 52 pacientes epilépticos de acompanhamento ambulatorial foi organizada por faixa etária de 12 a 30 e de 31 a 90 anos e, subdivididos por tempo de uso. As atividades séricas das GGT, FA, AST e ALT foram determinadas, assim como, as concentrações séricas da carbamazepina. As proporções de alterações por variáveis foram descritas. Resultados: 52% dos pacientes apresentaram alteração em pelo menos uma enzima, 42% com alterações nas FA, 18%, nas GGT, 12% nas AST e 2%, nas ALT. A faixa etária de 12 a 30 anos apresentou 56% de alterações nas FA enquanto que aquela de 31 a 90 anos, apenas 18%. Conclusão: a faixa etária pode colaborar com o aumento de prevalência das fosfatases alcalinas alteradas nestes pacientes. Quanto aos baixos valores para GGT e transamin
Carbamazepine is the drug utilized in the treatment of patients who bear epilepsy with secondary generalization. Furthermore, carbamazepine has been implicated with the serum increase of certain enzymes. Some authors have found a prevalence of 13% while others have found 22%, or even 53% of alterations for alkaline phosphatases. Objective: the goals of this study are to determine the ratio of alterations of the serum activities of the enzymes gamma-glutamil transferase (GGT), alkaline phosphatases (AF) and transaminases (AST, aspartate aminotransferase; and ALT, alanine aminotransferase) were determined as well as the serum concentrations of carbamazepine in samples taken from the metropolitan region of Salvador, Bahia. Methodology: the design of this study is descriptive and it has been approved by the local Ethics Committee. A convenience sample of 52 epileptic ward patients was distributed according to age groups of 12 to 30 and 31 to 90 years-old, and was also subdivided according to the period of usage. The serum activities of the enzymes GGT, AF, AST, and ALT were determined as well as the serum concentrations of carbamazepine. The proportions of alterations per variables were described. Results: 52% of the patients showed alteration in at least one enzyme, 42% with alterations in the AF, 18% in the GGT, 2% in the ALT, and 12% in the AST. The age group of 12 to 30 years-old showed 56% of the alterations in AF while the group of 31 to 90 year olds showed only 18% alterations. Conclusion: age group may contribute to the increase of prevalence of altered alkaline phosphatases in these patients. In regard to the low values 70 altered alkaline phosphatases In these patients. In regard to the low values of GGT and transaminases, futher studies would be necessary for better understanding of those variations.
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Qiu, Shi. "Effects of polymers on carbamazepine cocrystals phase transformation and release profiles." Thesis, De Montfort University, 2015. http://hdl.handle.net/2086/11421.
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The aim of this study is to investigate the effects of coformers and polymers on the phase transformation and release profiles of cocrystals. Pharmaceutical cocrystals of Carbamazepine (CBZ) (namely 1:1 carbamazepine-nicotinamide (CBZ-NIC), 1:1 carbamazepine-saccharin (CBZ-SAC) and 1:1 carbamazepine-cinnamic acid (CBZ-CIN) cocrystals, were synthesized. A Quality by Design (QbD) approach was used to construct the formulation. Dissolution and solubility were studied using UV imaging and High Performance Liquid Chromatography (HPLC). The polymorphic transitions of cocrystals and crystalline properties were examined using Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction (XRPD), Raman spectroscopy (Raman) and Scanning Electron Microscopy (SEM). JMP 11 software was used to design the formulation. It has been found that Hydroxupropyl methylcellulose (HPMC) cannot inhibit the transformation of CBZ-NIC cocrystals to Carbamazepine Dihydrate (CBZ DH) in solution or in the gel layer of the matrix, as opposed to its ability to inhibit CBZ Form III (CBZ III) phase transition to CBZ DH. The selection of different coformers of SAC and CIN can affect the stability of CBZ in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of the CBZ-SAC cocrystal can only be shown for 20 minutes during dissolution because of the conversion to its dihydrate form (CBZ DH). In contrast, the improved CBZ dissolution rate of the CBZ-CIN cocrystal can be realised in both solution and formulation because of its stability. The polymer of Hypromellose Acetate Succinate (HPMCAS) seemed to best augment the extent of CBZ-SAC and CBZ-CIN cocrystal supersaturation in solution. At 2 mg/ml of HPMCAS concentration, the apparent CBZ solubility of CBZ-SAC and CBZ-CIN cocrystals can increase the solubility of CBZ III in pH 6.8 phosphate buffer solutions (PBS) by 3.0 and 2.7 times respectively. All pre-dissolved polymers in pH 6.8 PBS can increase the dissolution rates of CBZ cocrystals. In the presence of a 2 mg/ml HPMCAS in pH 6.8 PBS, the cocrystals of CBZ-NIC and CBZ-CIN can dissolve by about 80% within five minutes in comparison with 10% of CBZ III in the same dissolution period. Finally, CBZ-NIC cocrystal formulation was designed using the QbD principle. The potential risk factors were determined by fish-bone risk assessment in the initial design, after which Box-Behnken design was used to optimize and evaluate the main interaction effects on formulation quality. The results indicate that in the Design Space (DS), CBZ sustained release tablets meeting the required Quality Target Product Profile (QTPP) were produced. The tablets’ dissolution performance could also be predicted using the established mathematical model.
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Santos, Niedja da Silva. "Chronic effects of carbamazepine on Danio rerio: a multi-parametric evaluation." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/18631.
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Mestrado em Toxicologia e EcotoxicologiaOs fármacos são atualmente considerados contaminantes ambientais emergentes, devido à sua constante deteção nos ecossistemas aquáticos, consequência do aumento na sua produção, diversificação e consumo. A carbamazepina (Cbz) é um fármaco humano utilizado para tratamento de epilepsia, distúrbios bipolares e neuralgia trigeminal estando entre os fármacos mais prescritos no mundo e sendo considerado um marcador de poluição antropogénica. Para uma correta avaliação de risco ambiental é essencial avaliar os efeitos a longo termo dos compostos em vários níveis de organização biológica. Assim, os objetivos deste trabalho foram: i) avaliar a toxicidade crónica da Cbz para o peixe-zebra (Danio rerio) adulto, numa gama de concentrações que inclui uma concentração ambientalmente relevante (10 μg.L−1) e uma concentração correspondente a 5% do valor de concentração letal mediana (CL50) (10000 μg.L−1). Foram estudados efeitos no crescimento, comportamento alimentar, reprodução (número total de ovos e viabilidade), defesas antioxidantes (atividade da catalase - CAT e Glutationa S- transferase - GST), neurotransmissão (atividade da acetilcolinesterase - AChE), atividade metabólica (atividade da lactato desidrogenase - LDH) e anomalias nucleares eritrocíticas nos adultos expostos a Cbz; ii) avaliar a toxicidade aguda do propranolol (Prop) (um fármaco cardiovascular utilizado no controlo da hipertensão, angina pectoris e arritmia após enfarte agudo do miocárdio) para adulto D. rerio após previa exposição a Cbz, iii) avaliar alterações na suscetibilidade de embriões decorrente da exposição aguda ao Prop após exposição parental a Cbz. A exposição crónica do peixe-zebra a Cbz induziu alterações no tempo total de ingestão de alimento nas duas concentrações testadas e induziu inibição da CAT no fígado e brânquias (10 e 10000 μg.L−1). A GST apresentou uma resposta dependente do órgão, com um aumento de atividade nas brânquias (10 e 10000 μg.L−1) e fígado (10000 μg.L−1) e diminuição no intestino (10000 μg.L−1). A atividade da AChE aumentou na cabeça (10 e 10000 μg.L−1) e músculo (10000 μg.L−1), enquanto a atividade da LDH apresentou-se aumentada no fígado (10000 μg.L−1) e diminuída no músculo e brânquias na concentração de Cbz mais elevada (10000 μg.L−1). Em termos reprodutivos, a Cbz (10 e 10000 μg.L−1) diminuiu o número de ovos viáveis produzidos por peixe-zebra. A prévia exposição de adulto D. rerio a baixas concentrações de Cbz (0 e 10 μg.L−1) induziu 100% de mortalidade quando os organismos foram expostos ao Prop (1000 e 5000 μg.L−1) enquanto, organismos expostos a maior concentração de Cbz (10000 μg.L−1) apresentaram capacidade para tolerar o Prop. A exposição crónica a Cbz não teve no entanto efeitos significativos na taxa de crescimento dos organismos, não tendo igualmente sido detectadas anomalias nucleares eritrocíticas, indicadores de cito e genotoxicidade. Os descendentes não demonstraram alterações na susceptibilidade ao Prop, quando comparados com os organismos controlo. De uma forma geral, os dados obtidos neste trabalho sugerem que a exposição crónica a baixas concentrações de Cbz afeta o comportamento e processos bioquímicos no peixe-zebra com possíveis consequências a nível da reprodução.
Pharmaceuticals are emerging environmental contaminants due to their constant detection into aquatic ecosystems, as a response to the increase in the rate of production, high diversity, and high consumption. Carbamazepine (Cbz) is used to epilepsy treatment, bipolar disorders, trigeminal neuralgia, being among the most prescribed drugs in the world and is considered a marker of anthropogenic pollution. For a correct environmental risk assessment, it is essential to evaluate the long-term effects of the compounds in various levels of biological organization. The objectives of this study were: i) evaluate the chronic toxicity (63 days) of Cbz for adult Danio rerio at an environmentally relevant concentration (10 μg.L-1) and at a concentration close to 5% of the median lethal concentration (LC50) value (10000 μg.L-1). Effects were studied on growth, feeding behavior, reproduction (total number of eggs and viability), antioxidant defences (Catalase - CAT and Glutathione-S-Transferase - GST), neurotransmission (acetylcholinesterase activity – AChE), metabolic activity (lactate dehydrogenase - LDH) and nuclear abnormalities in adults exposed to Cbz; ii) to evaluate the acute toxicity of propranolol (Prop) (a cardiovascular pharmaceutical used to hypertension control, angina pectoris and arrhythmia after acute myocardial infarction) for adult D. rerio after chronic exposure to Cbz, iii) to evaluate changes in offspring susceptibility to acute exposure to Prop after parental exposure to Cbz and, in offspring. Chronic exposure of zebrafish to Cbz induced changes in total time for food intake at the two concentrations tested. Cbz exposure induced changes in enzymatic activity: CAT was inhibited in the liver and gills (10 and 10000 μg.L-1); GST presented an organ-dependent response with increased activity in the gills (10 and 10000 μg.L-1) and in the liver (10000 μg.L-1) and a decrease in enzyme activity in the intestine (10000 μg.L-1); the activity of AChE was increased in head (10 and 10000 μg.L-1) and muscle (10000 μg.L-1); while LDH showed increased activity in the liver and decreased in muscle and gills, these effects were observed in the highest concentration of Cbz (10000 μg.L-1). The number of eggs produced did not suffer changes; however, the number of viable eggs produced by zebrafish, exposed to Cbz was reduced (10 and 10000 μg.L-1). The previous exposure of adult D. rerio to low concentrations of Cbz (0 and 10 μg.L-1) induced mortality of 100% when these organisms were exposed to Prop (1000 and 5000 μg.L-1) while organisms exposed to a higher concentration of Cbz (10000 μg.L-1) were able to tolerate the Prop.The chronic exposure to Cbz did not induced significant effects in growth rate of the organisms and no erythrocytic nuclear abnormalities, cito and genotoxicity indicators were detected. The offspring did not show changes in Prop susceptibility, when compared with the control organisms. Overall, the data obtained in this work suggest that chronic exposure to low concentration of Cbz affects feeding behaviour and biochemical processes in zebrafish with possible consequences at reproduction level.
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MONAT, THIERRY. "Effets cardiovasculaires des anti-epileptiques : revue de la litterature." Clermont-Ferrand 1, 1989. http://www.theses.fr/1989CLF13046.
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PUPESCHI, GERARD. "Criteres de reponse a la carbamazepine dans le syndrome maniaque : etude clinique et biologique." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX20136.
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Poletti, Jabbour Jamil, Rospigliosi Andrés Wiegering, Elías Reneé Pereyra, and Barrera Carmen Cecilia Elías. "Carbamazepine and oxcarbazepine: reflections after an oxcarbazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis overlap." Springer International Publishing, 2016. http://hdl.handle.net/10757/609483.
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Patel, Fathima. "The development and assessment of a generic carbamazepine sustained release dosage form." Thesis, Rhodes University, 2006. http://eprints.ru.ac.za/1339/.
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Lee, Jason Tsz Chun. "Prevention of type 1 diabetes by carbamazepine in non-obese diabetic mice." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62704.
Full textAbstract:
Pancreatic β cells are selectively destroyed by the host immune system in type 1 diabetes, which results in the inability to regulate glucose homeostasis due to loss of insulin production capacity. Drugs that preserve β cell mass and function therefore have the potential to prevent or slow the progression of this disease. It was recently reported by our group that the use-dependent sodium channel blocker, carbamazepine, protects pancreatic β cells from inflammatory cytokines in vitro. Subsequent experiments found carbamazepine increased insulin gene expression, which corroborated with an increase in insulin content in islets from mice lacking the Nav1.7 voltage gated sodium channel, which was shown to be a target of carbamazepine in β cells. While these in vitro results were promising, it was unclear whether carbamazepine would protect β cells in vivo against a complete immune system. Therefore, we tested the effects of oral treatment in female non-obese diabetic (NOD) mice, achieving serum carbamazepine levels of 14.98 ± 3.19 μM. Remarkably, diabetes incidence over 25 weeks was ~50% lower in carbamazepine treated animals. Partial protection from diabetes in carbamazepine-fed NOD mice was also associated with improved glucose tolerance at 6 weeks of age, prior to the onset of diabetes in our colony. Insulitis was improved in carbamazepine treated NOD mice at 6 weeks of age, but we did not observe differences in CD4⁺ and CD8⁺ T cell composition in the pancreatic lymph node, as well as circulating markers of inflammation. Taken together, our results demonstrate that carbamazepine reduces the development of type 1 diabetes in NOD mice.Medicine, Faculty of
Graduate
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Makmor, Bakry Mohd. "Influence of genetic variability on the clinical pharmacology of carbamazepine and lamotrigine." Thesis, University of Glasgow, 2007. http://theses.gla.ac.uk/1778/.
Full textAbstract:
This research programme investigates the influence of genetic variability on the clinical pharmacology of carbamazepine (CBZ) and lamotrigine (LTG). Common polymorphisms in genes that may influence the response to CBZ and LTG include CYP3A4 g.-392A>G, CYP3A5 g.6986A>G, CYP1A2 g.5734C>A, EPHX1 c.337T>C, EPHX1 c.416A>G, UGT2B7 c.802C>T, ABCB1 c.1236C>T, ABCB1 c.2677G>T/A, ABCB1 c.3435C>T and SCN2A c.56G>A. The prevalence of these common polymorphisms was evaluated in a 400-strong study population from a single research unit. Minor allele frequency ranged between 3.5% (CYP3A4 -392G) and 48.0% (ABCB1 1236T). Allele and genotype distributions were comparable to published data for other Caucasian populations. The influence of common polymorphisms in drug metabolising enzyme (DME) and sodium channel genes on the optimal dose of CBZ was assessed in a cohort of 70 patients. This study revealed that age and common polymorphisms in the EPHX1 gene (c.337T>C and c.416A>G) are potential predictors for optimal dose of CBZ. The significant effects of EPHX1 variants may be explained by their significant contribution to the inactivation of CBZ. These potential predictors explain approximately 15% of the inter-individual variation in CBZ dose requirements. Preliminary findings suggest that common polymorphisms in DME genes do not form a unique profile which increases the risk of developing intolerable CBZ adverse effects. It is unlikely that common polymorphisms in ABCB1 and SCN2A genes influence the expression and/or activity of their respective proteins to the level at which they can dictate response to LTG therapy. The influence of common polymorphisms in ABCB1 and SCN2A genes on the optimal dose of LTG was assessed in a cohort of 94 patients. Optimal dose in this study was defined as the final dose given to the patients that successfully maintained seizure freedom for at least 1 year with LTG monotherapy. Several basic clinical factors such as age and gender were also examined as potential predictors. The effect of predictors on the optimal dose of LTG was investigated using linear regression analysis. This study revealed that gender and common polymorphisms in the ABCB1 gene (c.1236C>T and c.3435C>T) are potential predictors for optimal dose of LTG. These predictors explain approximately 17% of the inter-individual variation in LTG dose requirement. These findings further highlight the potential role of P-gp in the management of epilepsy. The final study investigated the influence of ABCB1 c.1236C>T and ABCB1 c.3435C>T polymorphisms on the pharmacokinetics of LTG. A total of 156 blood samples from 50 patients receiving LTG monotherapy were available for analysis. The influence of ABCB1 variants was evaluated by population pharmacokinetics. This approach successfully estimated the oral clearance of LTG monotherapy at steady-state. However, the absorption rate constant (Ka) and volume of distribution (Vd) of LTG were poorly estimated. The inclusion of common polymorphisms in the ABCB1 gene in the pharmacokinetic model did not improve the estimation of oral clearance. This may indicate that common variants of ABCB1 do not influence clearance of LTG.
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Joshi, Onkar D. "Development of a solvent free continuous co-crystallisation technique for carbamazepine ¿ saccharin." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5697.
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Co-crystals are emerging as a potential area in the field of crystal designing as it
improves material¿s physicochemical properties. Many groups are working on the
development of newer techniques for the preparation of co-crystals, which can be scalable
and contribute to the green agenda. Being continuous and scalable technique, our own
developed twin screw extrusion mediated solvent free continuous co-crystallisation (SFCC)
technique has been used for the preparation of carbamazepine: saccharin co-crystal.
Carbamazepine has been used as a model drug since it shows challenges such as low
solubility (BCS class II), polymorphism and thermolabile nature whilst, saccharin was used
as a co-former.
Effect of extrusion processing parameters such as shear, temperature and screw speed on cocrystallisation
has been studied. In addition to this, effect of particle size of co-crystal
components, use of hydrated form of carbamazepine, addition of solvent and application of
reverse elements on the purity of co-crystal was understood. Use of carbamazepine dihydrate
as a starting component yields pure co-crystals. The addition of small amount of polar solvent
in anhydrous carbamazepine also yields pure co-crystals whereas particle size did not show
any significant effect. Result showed that selection of processing temperature near to eutectic,
moderate shear and increase in residence time of component mixture in mixing zone was
mainly responsible for co-crystallisation. The extrudates were mainly characterised by
XRPD, DSC and in-vitro dissolution tests. Pure co-crystals prepared by addition of highly
Development of a solvent free continuous co-crystallisation technique for carbamazepine-saccharin ii
polar solvent have been showed drug release identical to that of pure co-crystals prepared by
solvent crystallisation.
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Souza, Beatriz Pacheco de. "Avaliação de alterações cardiovasculares relacionadas ao efeito de drogas antiepilépticas em ratos submetidos ao modelo de indução de epilepsia pela pilocarpina." Universidade Federal de Goiás, 2018. http://repositorio.bc.ufg.br/tede/handle/tede/8603.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Epilepsy is one of the most common problems in the neurological clinic, affecting up to 1% of the world population, moreover, individuals with epilepsy have a higher mortality than the general population. Thus, the interest in investigating cardiac changes in patients with epilepsy has been increasing, and some studies have associated the use of antiepileptic drugs (AEDs) with cardiovascular disorders. In this context, there are hypotheses that patients using specific AEDs, sodium channel blockers, have an increased risk of cardiovascular disease (CVD). In our study, we sought to evaluate cardiovascular responses in epileptic rats submitted to chronic administration of carbamazepine (CBZ) or lamotrigine (LTG). Baseline cardiovascular parameters [Systolic blood pressure (SBP); Diastolic blood pressure (DBP); Mean arterial pressure (MAP) and heart rate (HR)] were recorded through cannulation of the femoral artery and electrode implant after sixty days of treatment with AED or vehicle [(150mg / kg (vo)]. The animals were submitted to a baroreflex test with bolus administration of phenylephrine (PHE - 5μg) and sodium nitroprusside (NPS - 10μg) via cannulation of the femoral vein and later submitted to a challenge with isoproterenol. Through the recording of baseline cardiovascular parameters, we also analyzed the heart rate variability (HRV) and the number of extrasystoles. After all procedures in vivo, samples of the heart were retained for histological analyzes of cardiac tissue. The division of the groups was performed in controls without epilepsy (CNT), epileptics (EP), epileptics treated with CBZ (CBZ) and epileptics treated with LTG (LTG). In our results the epileptic rats presented all the baseline cardiovascular parameters higher than the parameters of animals without epilepsy. CBZ treatment reduced resting HR, SBP and MAP compared to untreated epileptic animals. Treatment with LTG also reduced resting HR compared to the EP group. We also observed that the EP group had a greater cross-sectional area (CSA) of cardiomyocytes when compared to the other groups and an increased accumulation of perivascular collagen in comparison to CNT and CBZ groups. In this way, we can suggest that chronic use of AEDs may influence cardiovascular responses and cardiac microstructure.
A epilepsia é um dos problemas mais comuns na clínica neurológica, chegando a afetar até 1% da população mundial, além disso, indivíduos com epilepsia possuem uma mortalidade maior que a população geral. Com isso, o interesse em pesquisar alterações cardíacas em pacientes com epilepsia vem sendo crescente, e alguns estudos têm associado o uso de drogas antiepilépticas (DAEs) com distúrbios cardiovasculares. Neste contexto, há hipóteses de que pacientes em uso de DAEs específicas, bloqueadoras de canais para sódio, possuem aumento do risco de doença cardiovascular (DCV). Em nosso estudo, buscamos avaliar as respostas cardiovasculares em ratos epilépticos submetidos à administração crônica de carbamazepina (CBZ) ou lamotrigina (LTG). A divisão dos grupos foi dada em controles sem epilepsia (CNT), epilépticos (EP), epilépticos tratados com CBZ (CBZ) e epilépticos tratados com LTG (LTG). Os parâmetros cardiovasculares basais [Pressão arterial sistólica (PAS); Pressão arterial diastólica (PAD); Pressão arterial média (PAM) e Frequência cardíaca (FC)] foram registrados através de uma canulação da artéria femoral e do implante de eletrodos após sessenta dias de tratamento com DAEs ou veículo [(150mg/kg (v.o.)]. Durante o registro os animais foram submetidos a um teste de barorreflexo com administração em bolus de fenilefrina (PHE - 5μg) e nitroprussiato de sódio (NPS - 10μg) via canulação da veia femoral e posteriormente submetidos a um desafio com isoproterenol. Através do registro dos parâmetros cardiovasculares basais, também foi analisada a variabilidade da frequência cardíaca (VFC) e o número de extrassístoles. Após todos os procedimentos in vivo amostras do coração foram retiradas para análises histológicas do tecido cardíaco. Em nossos resultados os ratos epilépticos apresentaram todos os parâmetros cardiovasculares basais maiores que os parâmetros de animais sem epilepsia. O tratamento com CBZ reduziu a FC de repouso, PAS e PAM em comparação com animais epilépticos sem tratamento. O tratamento com LTG também reduziu a FC de repouso em comparação com o grupo EP. Também observamos que o grupo EP possui área de secção transversa (AST) de cardiomiócitos maior quando comparado aos demais grupos e maior acúmulo de colágeno perivascular em comparação aos grupos CNT e CBZ. Desta forma, podemos sugerir que o uso crônico de DAEs pode influenciar em respostas cardiovasculares e na microestrutura cardíaca.
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Tian, Fang, and n/a. "Towards a deeper understanding of the polymorphic conversion of carbamazepine in aqueous suspension." University of Otago. School of Pharmacy, 2007. http://adt.otago.ac.nz./public/adt-NZDU20070601.135438.
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Polymorphism can influence every aspect of the properties of a solid including the shelf life, dissolution rate, solubility, formulation properties and processing properties of a solid drug. A deeper understanding of polymorphism and related solid state properties would ensure an improved quality of the materials used throughout drug preparation, dosage form formulation and clinical trials. Therefore, determination of the existence of polymorphs and pseudopolymorphs, characterization of different solid state forms and their respective properties, and controlling the existing form in the resulting formulation all form part of a rapidly growing field within pharmaceutical research and industry.
Carbamazepine (CBZ) was the model drug used in this study. FT-Raman spectroscopy was chosen as a main investigative technique in this study to evaluate its potential in monitoring (pseudo)polymorphic conversions in aqueous suspensions in the absence or presence of various pharmaceutical excipients. Partial least squares analysis (PLS) was used for quantitative analysis of the spectral data.
Earlier it has been found that CBZ converts rapidly to the dihydrate (DH) when exposed to humidity or water, and this has been reported to be the main reason for the sometimes observed greatly decreased bioavailability of marketed CBZ tablets. In this study, the conversion kinetics of CBZ (forms I, II and III) to DH in aqueous suspension were found to be first order kinetics with an unconverted portion (R� [greater than or equal to] 0.95), where the crystal morphology appeared to play a more important role in its conversion kinetics than the polymorphic form. The influence of pharmaceutical excipients on the conversion of CBZ in aqueous suspension was also explored. For excipients such as methylcellulose (MC), hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) which have both a low solubility parameter (< 27.0 MPa[1/2]) and strong hydrogen bonding groups, complete inhibition of the conversion of CBZ was possible even at a very low concentration (0.1 % w/v).
Raman spectroscopy showed its high applicability in investigating CBZ conversion kinetics and screening of excipient effects in aqueous environment. It was demonstrated that Raman has a robust nature in quantitative analysis since problems such as different particle size, morphology, and spatial distribution of the two solid state forms of the drug seemed not to have significant influence on Raman scattering.
This study has also clarified the relative importance of many contributing factors (type of crystalline form (CBZ or DH), crystal morphology, surface area, and excipient interactions with drug particles) influencing the in vitro dissolution of CBZ. The solid state characterization approach taken in this study will provide a deeper insight into the dissolution performance of drugs and should thus lead to a better understanding of in vitro/in vivo behavior of drugs.
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Ju, Changqing. "Reactive iminoquinone metabolites of indomethacin and carbamazepine, implications for drug-induced idiosyncratic reactions." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0007/NQ41183.pdf.
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Wu, Ying. "Characterisation of the cellular basis of hypersensitivity reactions to carbamazepine and para-phenylenediamine." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430894.
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Qiao, Ning. "Investigation of carbamazepine-nicotinamide cocrystal solubility and dissolution by a UV imaging system." Thesis, De Montfort University, 2014. http://hdl.handle.net/2086/10201.
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In this study, the ability of pharmaceutical cocrystals on improving solubility and dissolution behaviour of poorly water soluble drug has been studied by a novel technique SDI300 UV imaging surface dissolution system. Pharmaceutical cocrystals of poorly water soluble drug carbamazepine (CBZ) were synthesized, which are 1: 1 carbamazepine - nicotinamide (CBZ-NIC) cocrystal, and 2:1 carbamazepine - succinic acid (CBZ-SUC) cocrystal. Firstly, dissolution and solution mediated phase transformation behaviour (SMPT) of CBZ-NIC cocrystal was studied by in situ techniques of UV imaging and Raman spectroscopy. This study has shown that in situ UV imaging and Raman spectroscopy with a complementary technique of SEM can provide an in depth understanding of cocrystal dissolution processes. It has been found that CBZ-NIC cocrystal including other polymorphs of CBZ III and I and mixture are converting to CBZ DH during dissolution. The influence of surfactants, SLS and Tween 80, on the solubility and dissolution behavior of the CBZ-NIC cocrystal has been studied. Results show that the SMPT of CBZ III and CBZ-NIC cocrystal can be altered by inclusion of a surfactant in dissolution medium. However, CBZ III and CBZ-NIC cocrystal have shown different transformation behavior with different surfactants. The solubility and dissolution behaviour of CBZ-NIC cocrystal, CBZ-SUC cocrystal in four biomedia (simulated gastric fluid, pH1.2 HCl buffer, simulated intestinal fluid, and pH 6.8 PBS buffer) were studied. Results have shown that equilibrium solubility of CBZ samples varied in different media. The two cocrystals dissolution rates show different trends as that of parent drug CBZ III. This can be explained by that the formation of cocrystal change the dissolution ability of CBZ III.
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Abd, Rahim Syarifah. "Understanding and predicting the physicochemical properties and crystallisation behaviour of carbamazepine co-crystals." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713468.
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The crystallisation and associated phase composition of carbamazepine (CBZ) co-crystals is presented with respect to the chemical nature of the co-crystal formers. Through an analysis of 50 structures representing three packing motif types, using both experimental and computational modeling, the respective physical properties are reviewed. Using a graded selection approach of increasing complexity, 3 CBZ co-crystals with succinic acid (SCA), aspirin (ASP) and saccharin (SAC) representing each of the known packing motif types are selected and their crystallisation and particulate properties examined. The co-crystal screening using stoichiometry and non-stoichiometry methods revealed that successful co-crystal formation depends on the method used in the screening, i.e. CBZ-glutaric acid forms a co-crystal in the stoichiometry method but not via the non-stoichiometric method. Two polymorphs of CBZSAC are obtained without the use of additive and the structure of CBZ-fumaric acid is solved. The synthon analysis from computational chemistry calculations revealed that van der Weals interaction make a significant contribution to the lattice energy with the hydrogen bonding interactions comprising both homosynthon and heterosynthon interactions with their respective strengths being affected by the electronegativity of the atoms involved. Slip planes calculations demonstrated that translational stack and conformer pairing packing have only one slip plane whereas, the inversion cup packing tend to have more. The predicted morphology revealed translational stack packing to be fine and thin needle-like whilst for inversion cup and co-former pairing packing a mixture of prismatic and thick needle-like morphologies is found. Cooling crystallisation studies revealed that CBZ-SCA and CBZ-SAC are easier to nucleate compared to CBZ-ASP whilst variation in co-crystal former content revealed no clear trend with respect to their crystallisability. Van't Hoff analysis based on solubility showed all carbamazepine co-crystals to exhibit comparatively have strong interactions between the solute and solvent. Crash cooling crystallisation demonstrated an increase in the induction time as the saturation temperature was increased for all the CBZ co-crystals with homogeneous nucleation dominant at high supersaturation. Particulate properties studies showed that CBZ-SCA has the highest mean particle size and better flowability compared to CBZ-ASP and CBZ-SAC.
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Catala, Isabelle. "Estimation des paramètres pharmacocinétiques de population de la carbamazépine en surveillance thérapeutique hospitalière." Montpellier 1, 1992. http://www.theses.fr/1992MON11103.
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BONNETON, VOLPI JOELLE. "Interaction medicamenteuse entre deux antiepileptiques majeurs : la carbamazepine et le valproate de sodium ; etude experimentale et clinique." Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX22963.
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Llorca, Pierre-Michel. "Efficacite comparee de la carbamazepine, de la bromocriptine, et de la cyproheptadine en traitement adjuvant aux neuroleptiques chez 24 patients schizophrenes chroniques resistants." Aix-Marseille 2, 1991. http://www.theses.fr/1991AIX20953.
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Zheng, Thomas Wen-Juan. "Neurophysiological and pharmacological study of carbamazepine on physiological and pathological GABAergic-dependent thalamocortical oscillations." Strasbourg, 2010. http://www.theses.fr/2010STRA6131.
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La CBZ est un anticonvulsivant largement prescrit, utilisé dans le traitement des épilepsies focales et de troubles psychiatriques. Cependant, il est connu que son large spectre d'action sur différentes cibles moléculaires contribue à des effets secondaires communs et sévères. La CBZ interagit directement avec les récepteurs GABAA, qui jouent un rôle critique dans l’électrogenèse d’oscillations TC/CT physiologiques et pathologiques. Mon travail de thèse offre des arguments solides pour dire que la CBZ module les propriétés de décharge et d’oscillations des neurones thalamiques, au moins dans le système somatosensoriel, au travers d’une augmentation des activités dépendantes de récepteurs GABAA. Ce mécanisme semble être le plus vraisemblable dans l’aggravation des absences. Le travail présenté dans cette thèse offre aussi d’importantes clés pour comprendre les mécanismes sous-tendant l'initiation et la propagation des DPO liées aux absences. Ces résultats mettent en évidence la présence d'activités de type précurseur dans S2 et IC durant l’électrogenèse des DPO. Il est donc tentant de mettre en avant l'hypothèse selon laquelle les aires corticales S2 et IC forment un circuit critique à partir duquel une excitation se propage dans des aires corticales interconnectées : S1, des aires corticales motrice et plus frontales. La propagation de cette excitation caudo-rostral pourrait être un élément neuronal clé dans l'initiation des crises d'absences. La CBZ est efficace chez les GAERS pour supprimer les DPO relatives aux absences uniquement lors d'une injection proche ou au niveau du site d'initiation présumé de cet embrasement excitateur caudo-rostralCBZ is a widely prescribed anticonvulsant used for the treatment of focal epilepsy and psychiatric disorders. However it is also known for its broad spectrum of action on several molecular targets contributing to common and severe side effects. CBZ directly interacts with GABAA receptors, which play a critical role in the generation of physiological and pathological TC/CT oscillations. My thesis work provides strong evidence that CBZ affects the firing and oscillation properties of thalamic neurons, at least in the somatosensory system, through enhancement of GABAA receptor-mediated activities, the likely mechanisms that underlie the aggravation of absence seizures. The work presented in this thesis also provides several important leads to mechanisms underlying the initiation and propagation of absence-related SWDs. The present findings demonstrate the presence of precursor cellular and network rhythmic activities in S2 and IC during the generation of absence-related SWDs. Therefore it is tempting to put forward the assumption that S2 and IC cortical areas contain a critical circuit from which excitation spreads to interconnected S1, motor and more frontal cortical areas. This spreading caudo-rostral excitation might be a key neuronal mechanism in the initiation of absence seizures. To all appearances CBZ is effective in suppressing absence-related SWDs
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Sampaio, Mariana Neiva. "The role of personality in fish response to Carbamazepine: from biochemical responses to learning." Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22022.
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Mestrado em Biologia Molecular e CelularA personalidade animal está ligada aos processos fisiológicos e bioquímicos do organismo. É definida como um conjunto individual de padrões comportamentais que se mantêm ao longo de um determinado período de vida. Estudos recentes mostraram a capacidade de muitos compostos, incluindo fármacos, interferirem no comportamento e em traços da personalidade. No entanto, o conhecimento sobre este fenómeno é ainda limitado. Sabendo-se que os fármacos podem interferir na personalidade, coloca-se a questão: qual será o papel da personalidade no efeito dos fármacos? Neste trabalho foi utilizado o peixe zebra (Danio rerio) como modelo biológico. Os organismos foram avaliados segundo parâmetros comportamentais e classificados e separados em dois grupos (bold e shy), com base no seu estilo de coping face a um novo ambiente. Como fármaco foi selecionada a carbamazepina, medicamento com elevada taxa de prescrição, detetado no ambiente e com uma reduzida taxa de degradação. Os organismos com os dois estilos de coping foram submetidos durante 96h a diferentes concentrações de carbamazepina (0.0044, 0.067, 1 e 15 mg/L). O estudo avaliou parâmetros comportamentais (e.g., distância total nadada e tigmotaxia) face a estímulos de luz (ciclos de luz e escuro) e biomarcadores bioquímicos. A aprendizagem e memória foram igualmente avaliadas com recurso a medições comportamentais diárias. Os dados obtidos revelaram diferenças nas respostas dos dois grupos de peixes, havendo um maior nível de atividade nos peixes reativos. As respostas aos períodos de luz/escuro foram diferenciadas. No escuro, a distância total nadada e a percentagem de distância nadada na área de fora são mais elevadas e a percentagem de tempo passado na área de fora foi menor. A carbamazepina por si só não influenciou as respostas analisadas. No entanto, as respostas dos peixes de diferentes personalidades dependeram das concentrações de carbamazepina a que estiveram expostos e do estímulo luz/escuro aplicado. Dos biomarcadores bioquímicos avaliados, LPO (peroxidação lipídica) variou de acordo com a personalidade, tendo os peixes proativos níveis mais elevados, e GST (glutationa-s-transferase) foi significativamente inibida nos peixes reativos pela maior concentração de carbamazepina. De uma forma geral os resultados mostram que estilos de coping influenciam a resposta a fármacos.
Animal personality is linked to physiological and biochemical processes of the organism. It is defined as individual behavioural patterns that are constant throughout a certain phase of life. Recent studies have shown compounds capacity, including pharmaceuticals, to interfere with behaviour and personality traits. However, knowledge about this phenomenon is still limited. Knowing that pharmaceuticals can interfere with personality, one question arises: what may be personality’s role on pharmaceutical’s effects? In this experiment, zebrafish (Danio rerio) was chosen as biological model. Individuals were evaluated by behavioural patterns and classified and separated in two groups (bold and shy) based on their stress coping strategy as a reaction to a novel environment. Carbamazepine was selected as pharmaceutical to study, due to its high prescription rate, detection in the environment and reduced degradation rate. Individuals with both coping styles were exposed for 96h to different concentrations of carbamazepine (0.0044, 0.067, 1 e 15 mg/L). The experiment evaluated behavioural parameters (e.g., total distance swam and thigmotaxis) in response to light stimuli (light and dark cycles) and biochemical biomarkers. Learning and memory were also evaluated resorting to daily behavioural measures. Data obtained revealed differences in responses between both groups of individuals. Behavioural data showed a higher activity level in shy fish. Responses to light and dark were also differentiated. In darkness, total distance swam and percentage of distance swam in the outside area increased comparing to light periods, whilst percentage of time spent in the outside area decreased. Carbamazepine alone did not influence responses analysed. However, responses from bold and shy fish depended on the concentration of carbamazepine and stimulus light/dark. From the biochemical biomarkers assessed, LPO (lipid peroxidation) varied according to personality, with bold fish having higher levels, and GST’s (glutathione-s-transferase) levels were significantly inhibited in shy fish exposed to the highest concentration of carbamazepine. Overall, results showed that coping styles influence response to pharmaceuticals.
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Sauvêtré, Andrés. "Uptake and metabolism of the antiepileptic drug carbamazepine in plants and role of endophytic bacteria." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/456572.
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Nuestro medio ambiente y reservas de agua reciben cada vez más productos de cuidado personal y fármacos. A pesar de una parcial degradación, algunos de estos compuestos presentan una eficiencia de eliminación muy baja en plantas convencionales de tratamiento de aguas residuales. En este contexto, el fármaco antiepiléptico carbamazepina (CBZ) es uno de los más recalcitrantes. Este producto se halla frecuentemente en aguas residuales, e incluso en los efluentes de las plantas de tratamiento de aguas residuales después del proceso de purificación, llegando a aguas superficiales y, en algunos casos, a las reservas de agua potable. Debido al incremento demográfico especialmente en áreas urbanas, es previsible en un futuro próximo la necesidad del uso de aguas residuales tratadas en lugar de agua subterránea. Por lo tanto, la eliminación de compuestos recalcitrantes será muy necesaria en el futuro para aliviar el estrés sobre el ciclo hídrico, el medio ambiente y los consumidores.
La fitorremediación es el tratamiento biológico de aguas residuales mediante plantas en humedales artificiales y representan una alternativa de bajo coste y sostenible para modernizar las plantas de tratamiento de aguas residuales existentes. Con esta tecnología, será posible eliminar estos contaminantes del agua residual tratada antes de su liberación al medio ambiente. Se ha puesto especial énfasis en el diseño de humedales artificiales para mejorar la eficiencia en la eliminación de compuestos peligrosos, incluyendo la selección de las especies vegetales más adecuadas o los programas de flujo hídrico. Otros estudios han considerado el papel de las comunidades microbianas del agua o de los sedimentos, pero se ha prestado poca atención a las comunidades endófitas asociadas a las plantas. Sin embargo, se ha demostrado recientemente la gran importancia del microbioma en el crecimiento de las plantas y su resistencia a estreses bióticos y abióticos.
En este trabajo se estudia la absorción y el metabolismo de CBZ utilizando una aproximación conceptual holobióntica en la cual bacterias endófitas seleccionadas interactúan con las plantas en beneficio mutuo. Plantas de carrizo común (Phragmites australis) fueron cultivadas hidropónicamente en solución Hoagland bajo condiciones controladas. Después de exposición a CBZ (5 mg/L) durante 9 días, un 90% del compuesto fue eliminado. Se extrajeron las bacterias endófitas de las raíces y rizomas de estas plantas y se identificaron mediante secuenciación del 16S rRNA. Además, se estudiaron sus características promotoras del crecimiento vegetal y su capacidad de eliminar CBZ. Diaphorobacter nitroreducens y Rhizobium radiobacter fueron seleccionados entre las cepas aisladas para un estudio de la absorción y metabolismo de CBZ en las raíces utilizando un cultivo axénico de raíz en cabellera de Armoracia rusticana como modelo.
Se identificaron un total de 13 productos de transformación mediante LC-QTOF-MS/MS. Estos metabolitos se clasificaron en 4 vías metabólicas diferentes. Un conjugado CBZ-glutatión fue detectado por primera vez en plantas. Armoracia rusticana preferentemente utilizó la vía del 10,11-diol y la del glutatión mientras que R. radiobacter y D. nitroreducens favorecieron las vías del 2-3-diol y de la acridina respectivamente.
CBZ indujo respuestas antioxidantes en el sistema de raíz en cabellera. Observaciones similares fueran realizadas en la activitad de glutatión-S-transferasas. El análisis proteómico evidenció el papel protector de las bacterias endófitas mediante un estímulo de la respuesta antioxidante cuando las plantas se enfrentan a estrés abiótico.
Podemos concluir que P. australis es una especie muy adecuada para la eliminación de CBZ en concentraciones relevantes desde un punto de vista ambiental y que esta degradación y eliminación del compuesto puede mejorarse a través del estímulo, de la presencia y funcionalidad de cepas beneficiosas seleccionadas entre la comunidad de bacteria endófitas.Our environment and our freshwater reserves suffer from increasing inputs of personal care products and pharmaceuticals. Despite partial degradation, some of these compounds have very low removal efficiency in conventional wastewater treatment facilities. The antiepileptic drug carbamazepine (CBZ) is one of the most recalcitrant compounds in this context. It is frequently found in wastewater, but also in the effluents of waste water treatment facilities after the treatment, reaches surface water and in some cases even drinking water reserves. With a growing urban population, forecasts are such that many of us will have to use reclaimed, treated wastewater instead of ground water. Hence, proper removal of recalcitrant compounds will be a necessity in the future to alleviate the stress put on the water cycle, the environment, and on consumers. Phytoremediation is the biological treatment of wastewater with plants in constructed wetlands and represents a cheap and environmental friendly alternative to retrofit existing waste water treatment facilities. With this technology it might be possible to remove these contaminants from treated wastewater before its release into the environment . Efforts have been put on the design of constructed wetlands to improve removal efficiencies of hazardous compounds, including the selection of best suited plant species or water flow regimes. Other studies have considered the role of microbial communities found in water or sediments, but little attention has been put into plant-associated and endophytic communities. However, the importance of the microbiome in plant fitness and resistance to biotic and abiotic stresses has been demonstrated recently. In this work, the uptake and metabolism of CBZ in plants is studied using a holobiontic conceptual approach in which plant and selected endophytic bacteria interact for mutual benefit. Common reed plants (Phragmites australis) were grown in liquid Hoagland solution under control conditions. After treatment with CBZ (5 mg/L) for nine days, up to 90% of the compound was removed. Endophytic bacteria were extracted from roots and rhizomes of these exposed plants, identified by 16S rRNA sequencing, and further characterized for their plant growth promoting traits and CBZ removal. Rhizobium radiobacter and Diaphorobacter nitroreducens were selected among the isolates for a comprehensive study of CBZ uptake and metabolism in interaction with plant roots. An axenic horseradish (Armoracia rusticana) hairy root (HR) culture was used as plant model to unravel which metabolic pathways are used for CBZ transformation by plants in the absence and presence of their endophytic partners. Inoculation with D. nitroreducens and R. radiobacter led to a 2-fold and 4-fold increase in the removal capacity oh HRs alone, respectively. In total, thirteen transformation products in the liquid media were identified by LC-QTOF-MS/MS. These metabolites were classified in four distinct metabolic pathways. For the first time, a CBZ-glutathione conjugate was detected in plants. Glutathione and 10,11-diol pathways were preferred by horseradish HRs while inoculation with R. radiobacter and D. nitroreducens favour the 2,3-diol and the acridine pathway respectively. A slight increase of ROS scavenging enzymes observed only in leaves tissues suggests that active metabolites formed in the root system by endophytic strains and plant cells are rapidly transported into the aerial part, inducing an antioxidant response in leaves followed by an increase in metabolic capacity of CBZ and its metabolites. GSTs were induced in rhizomes as well, indicating that the 10,11-diol and subsequent GSH pathways are the main metabolic pathways for CBZ degradation in P. australis. Antioxidant responses in HRs were induced by CBZ treatment but also after inoculation with endophytic bacteria. Similar observations were made on GST activities. The hypothesized protective role of endophytic bacteria when plants are confronted to abiotic stress by enhancing their antioxidant responses and detoxification mechanisms was evidenced by proteomics analyses. Superoxide dismutase, GR, monodehydroascorbate reductase, ascorbate peroxidase, all from the Halliwell-Asada cycle, were indeed identified in the growth media of inoculated roots. Additionally, proteomics results revealed a shift on HR metabolism from primary metabolism to structural and chemical defence processes after CBZ treatment. It can be concluded that P. australis is a species well-suited to remove CBZ at relevant environmental concentrations and that removal and degradation of the compound can be improved by enhancing the presence and functionality of selected beneficial strains among the endophytic bacterial community.
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Timsit, Yoav Ephraim. "Characterization of anti-cytochrome P450 antibodies in patients with carbamazepine hypersensitivity reactions, a mechanistic study." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29331.pdf.
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Bridgens, Rosalie Anne. "The role of counselling, monitoring of serum carbamazepine concentration, and of compliance in epilepsy control." Thesis, University of Limpopo (Medunsa Campus), 2012. http://hdl.handle.net/10386/1079.
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Thesis (MSc(Med)(Pharmacy))-- University of Limpopo, 2012.i THE ROLE OF COUNSELLING, MONITORING OF SERUM CARBAMAZEPINE CONCENTRATION, AND OF COMPLIANCE IN EPILEPSY CONTROL Non-compliance with the patient’s prescribed medication regimen has been identified in several publications as a major factor responsible for insufficient seizure control. Non-compliance is also held by some workers in this field to be closely interlinked with inadequate serum anti-epileptic drug concentration. The early identification of non-compliance may therefore play an important role in epilepsy therapy. A study was undertaken at Kalafong Hospital to explore the efficacy of monitoring serum carbamazepine concentration in order to detect compliance or otherwise. Intrinsic in such study was exploration of the role played by counselling in the promotion of compliance. Samples of blood were drawn from 78 outpatient volunteers at intervals as close to 28 days as possible, and the serum carbamazepine concentration of these samples was then determined by means of the TDx FLx System (ABBOTT). Items such as conscientious attendance at the Kalafong epilepsy clinics (“visits”), serum carbamazepine concentration, patient’s age, gender and weight, concomitant drug interactions, occurrence of epileptic seizures and dosage of Tegretol®CR were examined to ascertain whether they could be correlated with compliance and used as indicators thereof. It was, however, constantly borne in mind that these are not the only elements of compliance; other factors such as difficult fundamental behavioural changes, such as avoiding stress, may also play a part. Conscientious attendance at Kalafong epilepsy clinics (“visits”) was found to be a usable (albeit not strong) indicator of compliance. Serum carbamazepine concentration was used as another, with, however, reservations arising from the relationship between the patient’s actual compliance on the one hand, and whether v the daily dosage was sub-therapeutic or excessive on the other. The statistical agreement between visits and these concentration values was, however, very poor (8.2%). Using visits as an indicator, 66.7% of the participants were assessed as compliant. Using ‘compliant concentration’, only 25.6% were assessed as compliant. The data acquired during the study was, unfortunately, too variable to warrant anything more than descriptive statistical treatment. To a large extent this was because the participants were out-patients, not in-patients over whom strict therapeutic control could be exercised. Age, gender and patient’s weight were not significantly linked to compliance. The correlation between expected and measured serum carbamazepine concentrations was not statistically significant (p = 0.062). The Kalafong data in respect of seizures indicate that the relationship between seizures and compliance is not a simple one and that the occurrence or otherwise of break-through seizures should not be used as an indicator of compliance, as has indeed been done by other research workers. Drug interaction was as expected in 20 of the 26 patients concerned, this agreement being statistically significant (p = 0.0074). Improved compliance was the outcome expected from counselling but it was not possible to quantify the enhancement of compliance achieved, if any. Conventional verbal counselling, particularly when not done in the patient’s mother tongue and supported by interventions such as visual counselling material, may not be adequate.
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Galvão, Wilma Gomes. "CARBAMAZEPINA NO ESTADO SÓLIDO E SUA SUSCEPTIBILIDADE POLIMÓRFICA." Pontifícia Universidade Católica de Goiás, 2009. http://localhost:8080/tede/handle/tede/2115.
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Previous issue date: 2009-06-25Many pharmaceutical products are in solid state for reasons of stability or ease of handling during the stages of drug development. The polymorphism is the crystallization of the same substance in different crystalline architectures. This phenomenon is very common in pharmaceuticals and is associated with differences in packing arrangements of crystalline. The presence of different crystalline forms for the same drug can change some of its physicochemical properties such as solubility, which can directly affect their bioavailability and therapeutic efficacy. In this context, carbamazepine has served as a model compound for the study of polymorphism, where an analysis of its structural diversity has sought to evaluate the susceptibility polymorphic. Significant differences between the polymorphic forms of anhydrous carbamazepine were characterized by spectroscopic methods and difratometria, especially the X-ray diffraction, the important structural information provided. Where Polymorphic susceptibility to the more stable form can be observed due to several factors including the energy content is highlighted.
Muitos produtos farmacêuticos encontram-se no estado sólido por motivos de estabilidade ou por facilidade no manuseio durante as etapas de desenvolvimento da droga. O polimorfismo é a cristalização de uma mesma substância em diferentes arquiteturas cristalinas. Este fenômeno é muito comum em produtos farmacêuticos e está associado às diferenças nos arranjos da embalagem cristalina. A presença de diferentes formas cristalinas para um mesmo fármaco pode alterar algumas das suas propriedades físico-químicas, tais como a solubilidade, o que pode afetar diretamente sua biodisponibilidade e sua eficácia terapêutica. Neste contexto, a carbamazepina tem servido de composto modelo para o estudo do polimorfismo, onde uma análise de sua multiplicidade estrutural tem buscado avaliar a susceptibilidade polimórfica. Significantes diferenças entre as formas polimórficas anidras da carbamazepina foram caracterizadas por métodos espectroscópicos e difratométricos, em especial a difração de raios X, pelas importantes informações estruturais fornecidas. Onde a suscetibilidade polimórfica para forma mais estável pode ser observada em função de vários fatores entre eles se destaca o conteúdo energético.