Dissertations / Theses on the topic 'Drugs'
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Keesling, James Richard. "An evaluation of the drugs crime nexus, legalization of drugs, drug enforcement, and drug treatment rehabilitation." CSUSB ScholarWorks, 2000. https://scholarworks.lib.csusb.edu/etd-project/1697.
Full textApps, MIchael Garry. "Platinum anticancer drugs and drug delivery systems." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14409.
Full textOsorio, Javier. "Hobbes on drugs| Understanding drug violence in Mexico." Thesis, University of Notre Dame, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3738644.
Full textThis dissertation analyzes the unprecedented eruption of organized criminal violence in Mexico. To understand the dynamics of drug violence, this dissertation addresses three questions. What explains the onset of the war on drugs in Mexico? Once the conflict starts, why does drug violence escalate so rapidly? And lastly, why is there subnational variation in the concentration of violence?
Based on a game theoretic model, the central argument indicates that democratization erodes the peaceful configurations between the state and criminal organizations and motivates authorities to fight crime, thus triggering a wave of violence between the state and organized criminals and among rival criminal groups fighting to control strategic territories. In this account, state action is not neutral: law enforcement against a criminal group generates the opportunity for a rival criminal organization to invade its territory, thus leading to violent interactions among rival criminal groups. These dynamics of violence tend to concentrate in territories favorable for the reception, production and distribution of drugs. In this way, the disrupting effect of law enforcement unleashes a massive wave of violence of all-against-all resembling a Hobbesian state of war.
To test the observable implications of the theory, the empirical assessment relies on a novel database of geo-referenced daily event data at municipal level providing detailed information on who did what to whom, when and where in the Mexican war on drugs. This database covers all municipalities of the country between 2000 and 2010, thus comprising about 9.8 million observations. The creation of this fine-grained database required the development of Eventus ID, a novel software for automated coding of event data from text in Spanish. The statistical assessment relies on quasi-experimental identification strategies and time-series analysis to overcome problems of causal inference associated with analyzing the distinct - yet overlapping - processes of violence between government authorities and organized criminals and among rival criminal groups. In addition, the statistical analysis is complemented with insights from fieldwork and historical process tracing. Results provide strong support for the empirical implications derived from the theoretical model.
Hernández, Yulán. "Drugs." Revista de Química, 2016. http://repositorio.pucp.edu.pe/index/handle/123456789/101299.
Full textDossou-Yovo, Flore. "Modification de la biodisponibilité orale des médicaments : interactions « Herb-Drugs » « Drugs- Drugs»." Thesis, Paris, CNAM, 2014. http://www.theses.fr/2014CNAM0936/document.
Full textOral dosing is still seen as the silver bullet of drug administration, as it is cheaper andbetter adapted to patient comfort. However, oral route is still inaccessible to many drugssuch as biologics and biosimilars respectively certain anticancer drugs and antiretrovirals(ARV).The aim of this present study was to find new drugs enhancers that improve the oralbioavailability of drugs and xenobiotics. All the studies were realized in vitro using Ussingchambers technic. To achieve the set objective we used the strategy to develop drugenhancer which can modulate at the same time transcellular and paracellular pathways.In the first part of this study (patent) we have shown that the use of a pharmaceutical and /or a dietetic formulation containing a plant extract (Hibiscus sabdariffa) could increase thebioavailability in vitro in rats not only of cisplatin (21 fold), oxaliplatin (11 fold) andFluorescein Isothiocyanate-Dextran 4000 (FD4, 3 fold). All that drugs were transportedthrough intestinal barrier using paracellular pathway. In addition the study showed thatthis formulated enhancer can increased the bioavailability of Efavirenz (7 fold) andAtazanavir (4 fold) which are active transported.In order to assess the effect of new drugs enhancer on mucus thickness that limits thetransport of xenobiotic through intestinal barrier, we decide to evaluate his effect on passiveand active transport of drugs.In the second part of this study we have shown that after a week of pre-treatment of ratswith Metronidazole (MTZ, publication 1) and Cotrimoxazole (CTX, publication 2), the twomost commonly used antibiotics in the prophylaxis against opportunistic infections in HIV /AIDS, both increase colonic mucus thickness that affect directly passive intestinalpermeability by reducing conductance an index of passive transport through intestinalepithelium. In addition those antibiotics also entail a change in the transepithelialconductance and ARV fluxes. After MTZ and CTX treatment the secretion of Atazanavir(ATZ) increases respectively in the proximal colon by 2 to 4 fold and in the distal colon by 3to 5 fold respectively. Ritonavir (RTV) is poorly absorbed in control, after a week of pretreatmentwith MTZ and CTX one rather notices a secretion of RTV 5 to 10 fold higher in theproximal and 2 to 5 fold higher in the distal colon. The next study will be conducted toevaluate the effect of new drugs enhancer on mucus thickness layer.In conclusion, oral bioavailability of drugs and xenobiotics can be enhanced bypharmaceutical composition that contains herbal extract which increase passive and activetransport of drugs through intestinal barrier
Mohiddin, Syed Basha. "Development of novel unsupervised and supervised informatics methods for drug discovery applications." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1138385657.
Full textRosenbaum, Erik. "Optical characterization of potential drugs and drug delivery systems." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-40177.
Full textAttardo, Giorgio G. (Giorgio Giovanni). "Drug design and synthesis of novel heteroanthracycline antitumor drugs." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74641.
Full textAfter extensive studies, three methodologies were developed for the general synthetic plan. The first method involved photoenolisation of 2,5-dimethoxybenzaldehyde and SO$ sb2$ entrapment of the o-quinodimethane to give 4,7-dimethoxy-1-hydroxy-1,3-dihydrobenzo(2,3-c) thiophene-2,2-dioxide. This compound served as a general intermediate towards the synthesis of several heteroanthracyclinones. It could be reduced to the oxathiin-2-oxide derivative which thermally extruded SO$ sb2$ to yield the o-quinodimethane. Reentrapment of this latter intermediate with various glyoxalates gave key isochroman derivatives. The second method is an improvement over the first. Isochromandiones with a C-1 hydroxyl functionality were prepared from oxidative demethylation of 1-hydroxyisochromans. These were obtained after acid hydrolysis of the coupling products between epoxides and the cuprate of 2,5-dimethoxy-6-methylbenzaldehydedioxane acetal. The third method involved a sequential cycloaddition routine with two o-quinodimethanes.
By combining newly developed techniques with known methods, a general synthetic plan was developed. Consequently, the total synthesis of six tetracyclic structural hybrids of the naphthoquinone(2,3-c) pyranyl class of antibiotics was accomplished; along with the total synthesis of (R) and (S) 1-(4$ sp prime$-O-p-nitrobenzoyl-N-trifluoroacetyldaunosamine)-$ 1,3$-dihydrothioxantho(2,3-c) thiophene-2,2-dioxide, p-nitrobenzyl(5,12-dihydroxy-3,4-dihydrothioxantho(2,3-c) and (3,2-c) pyran-3-yl)formate, and eight novel heteroanthracyclines with the 5,12-dioxo-2,3,5,12-tetrahydroanthraceno(2,3-c) pyranyl backbone. The diastereomeric mixture of (1$ sp prime$S, 1R, 3S) and (1$ sp prime$S, 1S, 3R) methyl(11-hydroxy-1-$(2 sp prime,3 sp prime,6 sp prime $-trideoxy-3-trifluoroacetamido-L-lyxohexopyranose)-$5,12 $-dioxo-3,4,5,12-tetrahydroanthraceno(2,3-c) pyran-3-yl) formate was found to possess equipotent antileukemic activity to doxorubicin with no cross resistance.
Hill, John C. "DRUMMING AWAY DRUGS: AN INNOVATIVE ALTERNATIVE TOWARDS DRUG REHABILITATION." UKnowledge, 2014. http://uknowledge.uky.edu/cld_etds/14.
Full textHemingway, Judith Frances Mary. "Spatializing drugs discourses : cultural geographies of illicit drug-using." Thesis, University College London (University of London), 2003. http://discovery.ucl.ac.uk/10020432/.
Full textFoulkes, Broderick M. "Developing novel drug delivery methods for anti-leishmanial drugs." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/393974.
Full textThesis (Masters)
Master of Medical Research (MMedRes)
School of Medical Science
Griffith Health
Full Text
Zhang, Huarui. "Design, synthesis and activity evaluation of novel exosome inhibitors." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/849.
Full textNissen, Lisa Monique. "Quality use of medicines : from drug use evaluation to rural community pharmacy practice /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16549.pdf.
Full textTayob, Shamima. "Challenges in the management of drug supply in public health centres in the Sedibeng District, Gauteng Province." Thesis, University of Limpopo (Medunsa Campus), 2012. http://hdl.handle.net/10386/683.
Full textABSTRACT South Africa, 80% of the population is dependent on the vernment to provide for their health care needs, mainly ugh primary health care facilities. In the health objectives of the National Drug Policy, the government of South Africa outlines its commitment to ensuring availability and accessibility of medicines which are effective, affordable, safe and of good quality in all sectors of the health care system ( N a t ion a IDe par t men t of He a It h, 1 996) . In o rd e r to assess the availability of d ru g s and identify ch a II en g e s w hi c h . ex is tin the Emf u Ie n i sub - d is t r i c t wi t hi nth e Sedibeng district, a questionnaire was administered to 21 primary health care facility managers/store managers, fo u r Community Health Centre managers and five transport officers in the district. In addition, a document review process was conducted to verify aspects of th e facility managers' and store managers' responses. Bin cards and primary health care order files were also examined in conjunction with a checklist to establish whether stock control systems were in place. There was a 100% response with all primary health care centres and community health care centres completing th e questionnaires. It was established that drugs at primary and community health care clinics were procured from the Sedibeng district pharmacy. In each of these clin ics there were specific individuals responsible for medicine supply management. Only four primary health care clinics had full-time pharmacist assistants employed, and 14 clinics were visited by the assistants on a weekly/bi-weekly basis. There were no employees that have received training in drug supply management in the last 12 months in 88% of the clinics interviewed. Nineteen clinics claimed that the storage area was not large e n 0 ugh to s tor e a II the s toe k f or a m 0 nth's sup ply and 0 n I yon e clinic had a secure delivery area for their medication. It was established that 24 facilities received stock by two specific procedures namely; that the number of boxes were checked and the driver's note was then signed, and stock received was checked against the invoice. Of the interviewed cl i nics, 20% admitted that the re-order level had not been calculated for all tracer items in the store. Standard Operating Procedures, Standard Treatment Guidelines and the Essential Drugs List were also not available at all facilities. The results indicate inadequacies and weaknesses in procurement, quantification, stock control, storage and record keeping. It clearly demonstrates that inadequately-trained staff was a ma j 0 reo n t rib uti n g fa c tor to d rug s h 0 r tag e s. The r e was a I a c k 0 f monitoring and evaluation by th e district pharmacy as pharmacists did not manage to visit all the clinics each month. Most of the inadequacies and weaknesses can be addressed at facility level with pro per supervision, in-service training, mentoring and support of staff and the reinforcement of drug supply management training. Regular supervisory visits together with updating the monitoring too I in terms of th e problems identified will improve th e management of drugs and ultimately decrease the number of out of stocks where problems have been identified at primary health care level.
Hartmann, Neil Godfried. "Intercalative drugs in cancer chemotherapy : two approaches towards drug development." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292983.
Full textKaza, Lakshmi S. "Novel Thermal Analytical Techniques to Characterize Drugs and Drug Delivery." Cleveland State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=csu1317258017.
Full textKigen, Gabriel Kimutai. "Assessment of Drug Interactions Between Antiretroviral and the Anthelminthic drugs." Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507508.
Full textVaidya, B. K. "Chiral separation of drugs and drug intermediates by immobilized biocatalyst." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2009. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2773.
Full textMcCallum, Emma Clare. "Adaptive phase II clinical trial design using nonlinear dose-response models." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709013.
Full textWong, Ka Yeung Mark. "Drug clearance mechanisms and chemotherapy response." Thesis, The University of Sydney, 2007. https://hdl.handle.net/2123/28094.
Full textCarroll, Steven M. McGuire Marvin H. "The economics of the drug war : effective federal policy or missed opportunity? /." Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2002. http://library.nps.navy.mil/uhtbin/hyperion-image/02Jun%5FCarroll%5FMcGuire.pdf.
Full textTooley, Jennifer. "Demon drugs and holy wars, Canadian drug policy as symbolic action." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ54654.pdf.
Full textBanks, Simon. "Incompatibilities between HPMC and model drugs : consequences for extended drug release." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421473.
Full textJavaheri, Hoda. "Wet granulated liquisolid drug delivery systems with hydrophobic and hydrophilic drugs." Thesis, University of Sunderland, 2017. http://sure.sunderland.ac.uk/8549/.
Full textWheeler, Daniel Wren. "Weakened by strengths : drugs in solution, medication error and drug safety." Thesis, University of Oxford, 2008. http://ora.ox.ac.uk/objects/uuid:238087a5-120b-4a3d-9437-5840cecf8b6a.
Full textWang, Shining. "DRUG DEVELOPMENT OF TARGETED ANTICANCER DRUGS BASED ON PK/PD INVESTIGATIONS." Diss., Temple University Libraries, 2008. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/2535.
Full textPh.D.
EGFR inhibitors, such as gefitinib, are examples of targeted anticancer drugs whose drug sensitivity is related to gene mutations that adds a pharmacogenetic [PG] dimension to any pharmacokinetic [PK] and pharmacodynamic [PD] analysis. The goal of this project was to characterize the PK/PD properties of gefitinib in tumors and then apply these results to design rational drug design regimens, and provide a foundation for future studies with EGFR inhibitors. Progressions of in vitro and in vivo studies were completed to understand the PK and PD behavior of gefitinib. In vitro cytotoxicity assays were first conducted to confirm the gefitinib sensitivity differences in a pair of human glioblastoma cell lines, LN229-wild-type EGFR and LN229-EGFRvIII mutant, an EGFR inhibitor-sensitizing mutation. Subsequent in vitro PD studies identified phosphorylated-ERK1/2 (pERK) as a common PD marker for both cell lines. To describe the most salient features of drug disposition and dynamics in the tumor, groups of mice bearing either subcutaneous LN229-wild-type EGFR or LN229-EGFRvIII mutant tumors were administered gefitinib at doses of 10 mg/kg intravenously (IV), 50 mg/kg intraarterially (IA) and 150 mg/kg orally (PO). In each group, gefitinib plasma and tumor concentrations were quantitated, as were tumoral pERK. Hybrid physiologically-based PK/PD models were developed for each tumor type, which consisted of a forcing function describing the plasma drug concentration-profile, a tumor compartment depicting drug disposition in the tumor, and a mechanistic target-response PD model characterizing pERK in the tumor. Gefitinib showed analogous PK properties in each tumor type, yet different PD characteristics consistent with the EGFR status of the tumors. Using the PK/PD model for each tumor type, simulations were done to define multiple-dose regimens for gefitinib that yielded equivalent PD profiles of pERK in each tumor type. Based on the designed PK/PD equivalent dosing regimens for each tumor type, gefitinib 150 mg/kg PO qd × 15 days and 65 mg/kg PO qd × 15 days multiple-dose studies were conducted in wild-type EGFR and EGFRvIII mutant tumor groups, respectively. In each tumor group, gefitinib plasma and tumor concentrations were measured on both day 1 and day 15, as were tumoral amounts of pERK. Different from single-dose model simulations, gefitinib showed nonlinear PK property in the wild-type tumor due to the down-regulation of membrane transporter ABCG2. Moreover, acquired resistance of tumoral pERK inhibition was observed in both tumor types. Nevertheless, gefitinib had an analogous growth suppression action in both tumor groups, supporting the equivalent PD dosing strategy. Overall, single-dose gefitinib PK/PD investigations in a pair of genetically distinct glioblastomas facilitated the development of hybrid physiologically-based PK/PD models for each tumor type, and further introduced a novel concept of PK/PD equivalent dosing regimens which could be applied in novel drug development paradigms. Preliminary multiple-dose gefitinib studies revealed more complex PK/PD characteristics that needed to be further explored.
Temple University--Theses
MIELE, DALILA. "NANOPARTICLES AND NANOFIBERS AS DRUG DELIVERY SYSTEMS OF POORLY SOLUBLE DRUGS." Doctoral thesis, Università degli studi di Pavia, 2020. http://hdl.handle.net/11571/1321848.
Full textThe systemic route is the most common choice to administrate active molecules and to reach the therapeutic effect. Several limitations, including non-specific drug distribution, uncontrolled side effects and poor therapeutic efficacy that turn into toxic effects on sites different from the therapeutic target, mostly affect this route. For this reason, locally-released administration routes have recently attracted scientific research and novel systems aimed to carry therapeutic agents directly to specific cells or tissues are nowadays developed. In this context, nanomedicine and tissue engineering are broadly involved. These fields can work together in designing innovative and smart systems for in situ drug administration, solving all limitations linked to conventional drug delivery systems. Numerous studies have shown that nanoparticle and nanofibrous systems, obtained from natural and semi-synthetic biopolymers, are particularly effective in conveying poorly soluble or poorly bioavailable active ingredients. When properly functionalized or administered near the target site, both systems favor site-specific drug release, reducing systemic drug exposure, minimizing toxicity and improving its efficacy. The efficiency of these systems is linked either to the biomaterials employed, but especially to the high surface area given by the nanometric dimensions. Biocompatibility, biodegradability, and ability to be easily chemically modified are sought aspects during the formulation of this kind of nanosystems. This doctoral project is specifically aimed at developing novel polymeric nano-systems (nanoparticles, nanofibres and / or hybrid systems) able to improve biostability and bioavailability of poorly soluble drugs and guaranteeing a site-specific release.
Chan, Kin-yi Ivy. "A study of determinants of relapse in psychotropic substance abuse /." Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19470757.
Full textNaina, Mohamed Isa. "Novel approaches to pharmacovigilance : exploiting routinely acquired healthcare data." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=165979.
Full textMavridis, Lazaros. "High throughput virtual drug screening using spherical harmonic molecular surface representations." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=25936.
Full textYeh, Teng-Kuang. "Pharmacokinetics of anti-aids and anti-cancer drugs : implications on drug delivery and drug interaction /." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu148654688938101.
Full textBartu, Anne E. "A grounded study of the experience of detoxification from psychoactive drugs." Curtin University of Technology, School of Nursing, 1998. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=12124.
Full texttreatment, they lingered with the participants while they were in the unit, and remained to be addressed when they left. Whilst undergoing detoxification the participants encountered the second part of disequilibrium which was categorised as Incompatibility. The problem of Incompatibility was related to the heterogeneity of the participants and the structure of the treatment program that in many cases was unable to accommodate individual differences and needs.The core or basic social psychological process was conceptualised as Seeking Balance through Hanging In. The participants engaged in this process to deal with the disequilibrium of the precursor problem of Hitting the Wall and the problem of Incompatibility encountered in the unit. Seeking Balance through Hanging In was found to have four phases. The phases were Making the Break, Submitting to Cleansing, Fitting In, and Moving On. The process was linear in that the phases were sequential, and failure to complete a phase meant dropping out of the detoxification program. The experience of detoxification was modified by several contextual conditions. These were the physical enviroment, the participants' expectations of withdrawal symptoms, and the workload of the staff.The substantive theory, Seeking Balance through Hanging In, integrated all emergent categories, and explained the experience of the phenomenon of withdrawal from psychoactive drugs in a particular context. Recommendations for further research include testing the described phases and relationships of the substantive theory in similar environments, exploring the importance of the modifying conditions on client outcomes, and undertaking follow-up studies to determine the outcomes of those who completed the program as compared to the outcomes of those who dropped out. In addition, further studies are recommended to assess the transientness of the level ++
of minor psychiatric morbidity detected among the participants in this study.The findings of this study make an important contribution to understanding the experience of detoxification from the perspective of the participants. The substantive theory has implications for clinical practice, professional education, management, and further research.
Bartu, Anne. "A grounded study of the experience of detoxification from psychoactive drugs." Thesis, Curtin University, 1998. http://hdl.handle.net/20.500.11937/1748.
Full textBaker, Nicola Louise. "Screening for new natural drugs and drug resistance determinants in African trypanosomiasis." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590629.
Full textSoane, Robert J. "Bioadhesive polymers as intranasal drug delivery systems for peptide and protein drugs." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298078.
Full textKola-Mustapha, Adeola Tawakalitu. "Novel biomimetic polymeric nanoconjugates as drug delivery carriers for poorly soluble drugs." Thesis, De Montfort University, 2013. http://hdl.handle.net/2086/10243.
Full textSostelly, Alexandre. "Mechanistic model-based drug development in the management of anticancer drugs resistance." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10203.
Full textAnticancer drug resistance is a major issue in the management of cancer disease. Efflux transporters contribute to the multidrug resistance by altering the intracellular disposition of cytotoxic drugs. In the past, the inhibition of P-gp efflux transporter essentially failed because of the lack of adequate methods to identify their mechanisms of action. Recently, new inhibitors of BCRP, one of the latest efflux transporter that have been discovered, have been developed that allow re-testing the multidrug resistance inhibition through efflux inhibition. Nevertheless, to avoid the same issues of development as for P-gp inhibitors, new methods have to be used. This PhD work aims to demonstrate the benefits of mechanistic models to support the development of efflux transporter inhibitors and more generally of oncology compounds through two axes: - The development of mechanistic models of the interaction between cytotoxic and efflux transporter inhibitors - The development of quantitative tumour growth inhibition models to early evaluate oncology compounds and optimize patients’ response The results obtained with this approach allow the identification of key mechanisms of efflux transporter inhibitors and demonstrate the power of modelling and simulation to support oncology drug development
Moorad, Razia. "Computer-aided drug design and the biological evaluation of anti-cancer drugs." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20715.
Full textCoomber, Ross. "Perceptions of illicit drugs and drug users : myth-understandings and policy consequences." Thesis, University of Greenwich, 1999. http://gala.gre.ac.uk/8648/.
Full textPELLIZZONI, ELENA. "Molecularly imprinted polymeric nanoparticles for the therapeutic drug monitoring of anticancer drugs." Doctoral thesis, Università degli Studi di Trieste, 2016. http://hdl.handle.net/11368/2907991.
Full textChemotherapy consists in cancer treatment by the administration of a single or a combination of anticancer drugs. However chemotherapy agents are often characterized by an high variability of pharmacokinetic among patients and an high toxicity that leads to the appearance of many side effects decreasing the therapy efficiency. Therefore the therapeutic drug monitoring (TDM) become useful to develop personalized therapies for patients in order to increase the efficiency of the therapy and patient compliance. This project is aimed on the synthesis and development of specific sensors based on molecularly imprinted polymeric nanoparticles, to be applied in TDM of the anticancer drugs: sunitinib, paclitaxel, SN38 and its prodrug irinotecan. Soluble nanoparticles were obtained by high dilution radical polymerization with different functional monomers: N-acryloyl-tyrosine methyl ester, N-acryloyl-tryptophan methyl ester, 4-vinyl pyridine or 7-acryloyloxy-coumarin. The reactions were carried out allowing the functional monomer to interact with the drug by weak interactions (H-bonds, -staking and Van der Waals) in DMSO and after the addition of the co-monomer acrylamide, the crosslinker N,N’-ethylene bisacrylamide, and the radical initiator azobisisobutyronitrile (AIBN) the polymerization was achieved heating at 70°C for 4 days. The template was removed by dialysis first in methanol:acetic acid mixture and after in water. After the freeze-drying the polymers were characterized by 1H-NMR, Nanosight, and Dynamic Laser Light Scattering. The polymers binding capabilities and selectivity were investigated by rebinding tests using an HPLC method for the quantification of drug captured. while the fluorescence properties of some of these polymers were exploited to study the polymers binding affinities at low drug concentrations. The polymer containing coumarin and imprinted with sunitinib was used as fluorescence sensor to set up a validation test in DMSO:plasma mixture. The system showed an accuracy of 15%, a precision of 10% and a good robustness. Two different fluorescence sensors were also developed for irinotecan able to quantify the drug in methanol:plasma mixtures. The first sensor is based on the quenching of the intrinsic fluorescence of irinotecan, while the second is an highly fluorescence polymer containing a functional monomer with a naphthalimide mojety whose fluorescence is quenched upon interaction with the drug. Moreover the dye displacement technique was used to set up a fluorescent and colorimetric test for paclitaxel quantification. The test is based on the competition between the free paclitaxel and the drug covalently linked to DABCYL dye, for the binding in to an imprinted polymer containing EDANS fluorescent functional monomer. Since DABCYL is both a red dye and a FRET quencher of EDANS, its binding into the polymer gives a change in the polymer fluorescence and colour. Finally a colorimetric test for irinotecan quantification was developed using an imprinted polymer containing 2-acrylamido-2-methylpropane sulfonic acid as functional monomer. The test is based on the binding of aniline yellow dye in to the remaining free binding sites of the polymer after treatment with drug samples. The interaction between the dye and the sulfonic acid in to the polymer gives a change of colour from yellow to red.
IACUZZI, VALENTINA. "Design of detection systems for the therapeutic drug monitoring of anticancer drugs." Doctoral thesis, Università degli Studi di Trieste, 2020. http://hdl.handle.net/11368/2967986.
Full textDespite the continuous progress in drug therapy, most anticancer drugs appear to be characterized by a high interindividual variability in plasma concentrations that is reflected in the efficacy of the treatment. From this arises the need of a personalized approach, so that the drug concentrations in plasma are adequate in each patient. On this basis, during the PhD project reported hereby, different techniques for therapeutic monitoring (TDM) of anticancer drugs were developed. First, a LC-MS/MS method for the quantification of imatinib (IMA) and its active metabolite, norimatinib (norIMA), was developed, validated and cross-validated in patients affected by gastrointestinal stromal tumour. This method allows to perform the quantification directly on a drop of capillary blood, exploiting the dried blood spot (DBS) technique, reducing sampling time, costs and improving patients’ compliance. Analytes were extracted from DBS samples by adding acidified methanol and the extract is injected into a LC system (configured with a 2D chromatography for online cleaning of the sample), coupled with an API-4000QT. The method showed good linearity (R2> 0.996) in the ranges of 50-7500 ng/mL and 10-1500 ng/mL for IMA and norIMA. Intra-day precision and accuracy were ≤3.1% and between 88.9-112.8%, respectively, while inter-day ones were ≤6.6% and between 95.7-104.3 %, for both analytes. Moreover, were also evaluated: the influence of the haematocrit (Hct), of the spot size and of the sample homogeneity on the analysis; the correlation between the concentration in DBS from venous sampling and from finger-prick (% difference between -12 and 3.8%) and the stability of DBSs (up to 16 months). Then, the method was applied for the quantification of 67 DBSs patients’ samples. Good agreement was obtained between IMA and norIMA concentrations found in DBS and plasma samples applying either the Hct normalization or avoiding it, simply multiplying the DBS concentration with a correction factor. Part of the work of this project was also dedicated for the development of alternative strategies for the quantification of anticancer drugs, to promote the application of TDM. In particular, the synthesis of molecularly imprinted polymers (MIPs) was performed, with the future goal of applying them as receptors in a fluorimetric detection system for IMA. MIPs were synthesized using the non-covalent approach and high dilution radical polymerization. Through this synthesis, the MIPs obtained, synthesized in DMSO with methacrylic acid as functional monomer, shown nanometric size (data acquired by dynamic light scattering). The rebinding tests then showed that 2 MIPs in particular were able to bind IMA with a good specificity (compared to the corresponding non-imprinted polymers) and selectivity. Finally, a LC-MS/MS method was developed and validated for the quantification of ribociclib (RIBO), palbociclib (PALBO) and letrozole (LETRO) in human plasma. RIBO and PALBO are drugs belonging to the CDKIs family, recently approved for breast cancer treatment in combination with LETRO. The method developed is suitable for its application in clinical practice, thanks to simple sample preparation and rapid analysis (6.5 min). The method showed a good linearity (R2 between 0.992-0.983) in the concentration ranges of 0.3-250 ng/mL for PALBO, 10-10000 ng mL for RIBO and 0.5-500 ng/mL for LETRO (covering the therapeutic plasma concentrations). Intra-day precision and accuracy were ≤3.6% and between 94.5-112.3% for all and analytes, respectively, while inter-day ones were ≤ 7.3% and 94.5-112.9%. The method has been successfully applied for patients’ plasma samples quantification. In conclusion, with the development of these strategies there is the hope to implement the application of TDM for anticancer drugs in the clinical practice.
Stephen, Linda J. "Antiepileptic drugs - treating populations." Thesis, University of Glasgow, 2010. http://theses.gla.ac.uk/2005/.
Full textLi, Jian. "Ciliotoxicity of intranasal drugs." Thesis, Queen's University Belfast, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317473.
Full textRidout, G. "Percutaneous absorption of drugs." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373320.
Full textWalker, Teneille. "Therapeutic Drugs in Cancer." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1722.
Full textWilliams, Kylie Anne. "Pharmacoepidemiology of nonprescription drugs." Thesis, The University of Sydney, 1998. https://hdl.handle.net/2123/27671.
Full textMenjoge, A. R. "Enhancing bioavailability of drugs." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2006. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/2512.
Full textMahaguna, Vorapann. "Investigation of cellulose ether polymers in controlled drug delivery." Access restricted to users with UT Austin EID Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3037524.
Full textJoshua, Isaac B. "The impact of an intervention program for the treatment of malaria in children in Papua New Guinea." Thesis, Curtin University, 2003. http://hdl.handle.net/20.500.11937/2339.
Full textCrispim, Rute Irene Claudio. "Impact of the national drugs politics (NDP) in the access the gratuitous Drugs." Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1907.
Full textThis work aims at the investigation of access to medicines free for users of SUS through the National Drug Policy. The database was used to PENAD98/03. In this research used is a model that conceitua access according to the individual use of the public health service, and receiving the medicine free taking into account the characteristics that lead to use those services. Through Logist model by the method of maximum likelihood has been unable to verify that access to free medicines rose between 6% and 9 percentage points five years after the promulgation of the PNM. The descriptive review with respect to the receipt of free product per lane-income, shows that even among users of SUS, those with higher incomes have a lower probability of receiving free medication. And for the carriers of chronic diseases such as diabetes and hypertension, are more likely to receive free medicine. These results show some effectiveness of the public service to reach those who are really in need.
Este trabalho tem como objetivo a investigaÃÃo do acesso aos medicamentos gratuitos para usuÃrios do SUS por meio da PolÃtica Nacional de Medicamentos. A base de dados utilizada foi a PENAD98/03. Nesta pesquisa utilizou-se o modelo que conceitua acesso de acordo com a utilizaÃÃo do individuo ao serviÃo pÃblico de saÃde, e recebimento do medicamento gratuito levando em conta as caracterÃsticas que levam a utilizar esses serviÃos. Mediante modelo Logist atravÃs do mÃtodo de mÃxima verossimilhanÃa foi possÃvel verificar que o acesso a medicamentos gratuitos aumentou entre 6 e 9% pontos percentuais cinco anos apÃs a promulgaÃÃo da PNM. A analise descritiva com relaÃÃo ao recebimento de medicamento gratuito por faixa de renda, mostra que mesmo entre os usuÃrios do SUS, aqueles com maiores rendimentos tÃm uma probabilidade menor de receber medicamentos gratuitos. E para os portadores de doenÃas crÃnicas como diabetes e hipertensÃo estes, tÃm maiores chances de receberem medicamentos gratuitos. Estes resultados demonstram certa eficÃcia do serviÃo pÃblico de atingir aqueles que realmente sÃo mais necessitados.