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Auswahl der wissenschaftlichen Literatur zum Thema „Metabolismus léčiv“
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Zeitschriftenartikel zum Thema "Metabolismus léčiv"
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Matalová, Petra, und Michal Buchta. „Specifics of Metabolism in Children“. Klinická farmakologie a farmacie 34, Nr. 4 (22.12.2020): 159–66. http://dx.doi.org/10.36290/far.2020.027.
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Tománková, Veronika, Adéla Vlčková, Pavel Anzenbacher, Petr Bachleda und Eva Anzenbacherová. „The use of goldenrod general (Solidago virgaurea) preparations does not influence the metabolism of concomitantly administered drugs“. Klinická farmakologie a farmacie 30, Nr. 1 (30.05.2016): 5–10. http://dx.doi.org/10.36290/far.2016.002.
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Moserová, Michaela. „Metabolismus karcinogenů a léčiv monooxygenasovým systémem“. Doctoral thesis, 2011. http://www.nusl.cz/ntk/nusl-311556.
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Ellipticine, an alkaloid isolated from Apocynaceae plants, exhibits significant antitumor and HIV activities. Ellipticine is a pro-drug, whose pharmacological and genotoxic effects depend on activation by cytochromes P450 (CYP) and peroxidases (Px) to a reactive species generating DNA adducts. To elucidate contribution of CYPs (and which of them) and Px to ellipticine activation, we used rat and mouse models, mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting this enzyme in the liver (HRNTM ) and a control mouse line (WT), rats treated with ellipticine, and microsomal systems isolated from the liver of mouse lines and from the liver, kidney and lung of rats. The purified enzymes, CYP1A1 and 3A4, reconstituted with NADPH:CYP reductase were also used. The effect of cytochrome b5, a facultative component of the mixed function monooxygenase system, on ellipticine oxidation by CYP1A1 and 3A4 was also investigated. Carcinogenic benzo(a)pyrene (BaP), known to covalently bind to DNA after its activation with CYPs, was investigated for its potential to generate DNA adducts and to induce CYP and NADPH:CYP reductase enzymes in mouse livers. We investigated an influence of each of components of the mixed function oxidases (MFO) system on metabolism of BaP. CYP1A1 is widely accepted to be the...
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Wilhelm, Marek. „Vliv cytochromů P450 na metabolismus protinádorových léčiv vázaných v apoferritinové nanočástici“. Master's thesis, 2020. http://www.nusl.cz/ntk/nusl-434077.
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Tumour-related diseases are the second most common cause of death in the Czech Republic, right after cardiovascular diseases. Nanomedicine - a novel scientific discipline - shows captivating potential in anticancer treatment with help of so called nanotranporters - nanoparticles capable of transporting other molecules. Encapsulation of a cytostatic drug into a nanoparticle improves its pharmacokinetical and pharmacodynamical properties which helps to reduce adverse side effects on non-tumour healthy tissue. In the scope of this diploma thesis apoferritin - apo-form of ferritin - was studied, since this nanotransporter shows promise for clinical use in anticancer treatment. Effect of hepatic microsomes from premedicated and control rats on biotransformation of doxorubicin cytostatic (Dox) in free and apoferritin nanoparticle-bound forms was investigated at pH 7,4. Over the course of biotransformation two types of metabolites - M1 and M2 - were observed. Regardless of the employed inductor all studied microsomes have exhibited similar metabolism of free doxorubicin and its apoferritin encapsulated form (ApoDox). Our results also imply that doxorubicin can be metabolically processed by rat hepatic microsomes in both free and ApoDox form with similar efficiency. We have also studied biotransformation...
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Mrízová, Iveta. „Úloha systému oxidas se smíšenou funkcí s cytochromem P450 v metabolismu léčiv a karcinogenů“. Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-353595.
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6 Abstract Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), an alkaloid isolated from Apocynaceae plants, exhibits significant antitumor and HIV activity. This antitumor agent binds to DNA and forms covalent DNA adducts. Enzymes, which are involved in its enzymatic activation, are cytochromes P450 (CYP) and peroxidases. To elucidate the effect of ellipticine on the expression and enzymatic activity of the individual components of the microsomal mixed function oxidase system in different tissues, we used rat model. Simultaneously, the effect of ellipticine and its cytotoxicity on different tumor cell lines was also investigated. Another part of the presented work was targeted on preparation of anti-peptide antibody against orphan cytochrome P450 2S1, which is highly expressed in many human tumours of the epithelial origin, for its detection in these tissues. For better understanding how CYP2S1 can contribute to the metabolism of xenobiotics, the protein was prepared by heterologous expression in E. coli. Furher, its role in metabolism of an antitumor drug ellipticine, a carcinogenic environmental pollutant benzo[a]pyrene (BaP) and its derivate BaP-7,8-dihydrodiol was examined. Utilizing a mouse model, the impact of pulmonary inflammation on the metabolism of an environmental carcinogen was...
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Dobečka, Kryštof. „Experimentální přístupy pro studium jaterní enzymatické indukce zprostředkované pregnanovým X receptorem“. Master's thesis, 2021. http://www.nusl.cz/ntk/nusl-446103.
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Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kryštof Dobečka Supervisor: PharmDr. Tomáš Smutný, Ph.D. Advisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Experimental approaches for studying hepatic enzyme induction mediated by pregnane X receptor The thesis focuses on hepatic pregnane X receptor (PXR)-mediated induction of biotransformation enzymes. Emphasis is placed on experimental models and methods which are used for the assessment of enzyme induction. In addition to summarizing its well- established role as a xenobiotic-sensing receptor, PXR is also presented as a transcription factor with an important role in endogenous pathways. Furthermore, cell and animal models are evaluated in terms of expression and function of PXR and its target xenobiotic-metabolising enzymes. Primary human hepatocytes in 2D cultures are considered to be the gold standard of in vitro hepatic models. However, 3D technologies are expected to be increasingly used in the future. The use of animal models is limited due to pronounced interspecies differences in PXR activation. Thus, humanized models have been established to overcome these limitations. Next, this thesis comments screening methods for an assessment of interaction between PXR and...
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Hromek, Vlastimil. „Studium metabolismu inhibitorů tyrosinkinas, protinádorových léčiv nové generace“. Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-343403.
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Vandetanib is an oral anticancer drug, acting as tyrosinkinase inhibitor of a number of cell receptors. It targets to cell receptors, which are responsible for a development and proliferation of medullary thyroid cancer. This drug was approved by FDA (US Food and Drug Administration) for a treatment of late-stage (metastatic) or a progressive medullary thyroid cancer at patients who are ineligible for a surgery. Recent studies indicate that one of problems with the vandetanib therapy is its biotransformation in human organism. This thesis investigates metabolism of vandetanib. Human and rat hepatic microsomes as well as rat and human cytochromes P450 (CYPs) and flavin monooxygenases expressed in SupersomesTM were used for this study. During experiments rat hepatic microsomes isolated from both the uninduced rats and animals in which indiviual CYPs expression was increased by CYP inducers were used. The metabolites formed from vandetanib were separated by HPLC and identified by mass spectrometry. The formed metabolites were identified as N- desmethylvandetanib and vandetanib N-oxide. Vandetanib N-oxide was generated by all tested microsomes. The highest amount of N-desmethylvandetanib was produced by microsomes of rats pretreated with pregnenolon carbonitrile (PCN that is an inducer of CYP3A). This...
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Suchanová, Bohumila. „Univerzální využití kapalinové chromatografie a hmotnostní spektrometrie v metabolismu léčiv“. Doctoral thesis, 2007. http://www.nusl.cz/ntk/nusl-271007.
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Human organism has always been exposed to a vast array of chemicals encountered in the environment. Chemical revolution has significantly influenced biological evolution of humans leading to serious unpredictable toxicities. In response to continual chemical stress they have developed a variety of enzymes to transform these xenobiotics. Xenobiotics are mostly highly lipophilic and cannot readily be excreted from the body without metabolism to more hydrophilic, water-soluble metabolites. Not only environmental chemicals represent xenobiotics but also drugs, dietary components etc. Biotransformation studies play an important role in the drug discovery and development process. Usually data from drug metabolism is required before a new substance can advance towards the development stages of a new therapeutic agent. Data on metabolism is frequently used to optimize drug candidates, suggest more active compounds or support toxicology studies. The increased flux of new chemical entities into drug discovery has placed an increased need for fast and reliable information on the metabolism of these substances. Liquid chromatography coupled with mass spectrometry can meet demands for rapid drugs and metabolites analysis imposed by modern drug discovery strategies. This dissertation thesis presents an evidence...
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Háčková, Markéta. „Metabolismus protinádorového léčiva ellipticinu v cílových tkáních jeho účinku“. Master's thesis, 2008. http://www.nusl.cz/ntk/nusl-358420.
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Vavrová, Katarína. „Metabolismus inhibitoru tyrosinkinas lenvatinibu jako protinádorového léčiva s cílenými účinky“. Master's thesis, 2018. http://www.nusl.cz/ntk/nusl-379364.
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Lenvatinib is an oral anticancer drug that belongs to a group of tyrosine kinases, which block signal pathway receptors for development and proliferation of various cancer diseases. Lenvatinib was approved in 2015 for a treatment of progressive, locally spread or metastatic, differentiated thyroid cancer refractory to radioiodine treatment. This thesis presents findings about the metabolism of lenvatinib and identification of enzymes responsible for biotransformation of this drug. Utilizing human and rat hepatic microsomes as well as recombinant cytochromes P450 (CYPs) expressed in SupersomesTM , the metabolism of lenvatinib was studied. Used rat microsomal systems were isolated from the liver of uninduced rats and from the liver of rats in which expression of individual CYPs was induced by CYP inducers. The lenvatinib metabolites were separated by HPLC and identified by mass spectroscopy. Using rat microsomal systems, O-desmethyllenvatinib and lenvatinib N-oxide were produced. The highest amount of these lenvatinib metabolites was produced by microsomes of rats pretreated with pregnenolone carbonitrile that is an inducer of CYP3A. Human hepatic microsomes oxidize lenvatinib to O-desmethyllenvatinib and N-descyklopropyllenvatinib. In the case of rat recombinant CYPs, O-desmethyllenvatinib was...
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Hronová, Karolína. „Polymorfismus genů účastnících se v metabolismu léčiv jako potencionální cíl prevence závažných komplikací léčby u novorozenců a dětí“. Doctoral thesis, 2018. http://www.nusl.cz/ntk/nusl-389807.
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Univerzita Karlova 1. lékařská fakulta Studijní program: Biomedicína Studijní obor: Preventivní medicína MUDr. Karolína Hronová Polymorfismus genů účastnících se v metabolismu léčiv jako potenciální cíl prevence závažných komplikací léčby u novorozenců a dětí Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants Disertační práce- ABSTRAKT V ANGLICKÉM JAZYCE Školitel: prof. MUDr. Ondřej Slanař, Ph.D. Konzultant: MUDr. Pavla Pokorná, PhD. Praha, 2018 Abstract Background and aims: The safety of analgosedative drugs includes drug interactions, adverse effects, withdrawal syndrome and drug dependence are factors that significantly affect morbidity and mortality. Its prevention is critical for quality improvement of care in paediatric patients. The aim of the thesis was to evaluate the prediction of efficacy and safety of analgosedative drugs sufentanil, midazolam, tramadol and valproic acid in neonates and children based on the occurrence of selected pharmacogenetic biomarkers. The incidence of drug interactions of phenobarbital with other analgosedative drugs has also been evaluated. Methodology: The thesis is based on two studies conducted on Intensive and Resuscitation Care Unit of the Clinic of Paediatric and Adolescent...
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Kotrbová, Věra. „Studium aktivačního a detoxikačního metabolismu protinádorového léčiva ellipticinu systémem cytochromů P450 in vitro a in vivo…“. Doctoral thesis, 2008. http://www.nusl.cz/ntk/nusl-274194.
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Gen. Physiol. Biophys. (2006), 25, 245-261 245 Oxidation Pattern of the Anticancer Drug Ellipticine by Hepatic Microsomes - Similarity Between Human and Rat Systems M. Stiborová1 , L. Bořek-Dohalská1 , D. Aimová1 , V. Kotrbová1 , K. Kukačková1 , K. Janouchová1 , M. Rupertová1 , H. Ryšlavá1 , J. Hudeček1 and E. Frei2 1 Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic 2 Division of Molecular Toxicology, German Cancer Research Center, Heidelberg, Germany Abstract. Ellipticine is an antineoplastic agent, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerase II and formation of DNA adducts mediated by cytochrome P450 (CYP). We investigated the ability of CYP enzymes in rat, rabbit and human hepatic microsomes to oxidize ellip- ticine and evaluated suitable animal models mimicking its oxidation in humans. Ellipticine is oxidized by microsomes of all species to 7-hydroxy-, 9-hydroxy-, 12- hydroxy-, 13-hydroxyellipticine and ellipticine N2 -oxide. However, only rat micro- somes generated the pattern of ellipticine metabolites reproducing that formed by human microsomes. While rabbit microsomes favored the production of ellipticine N2 -oxide, human and rat microsomes predominantly formed 13-hydroxyellipticine. The species difference in...