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Dissertations / Theses on the topic 'Human liver microsomes'

Author: Grafiati

Published: 4 June 2021

Last updated: 25 January 2023

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1

Emery, Maurice George. "Aspects of human CYP 2E1 regulation in health and disease /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/7943.

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2

McLure, James Alexander, and james mclure@flinders edu au. "Physicochemical determinants of the non-specific binding of drugs to human liver microsomes." Flinders University. Medicine, 2008. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20081102.165952.

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Accurate determination of the in vitro kinetic parameters Km (Michaelis constant) and Ki (inhibition constant) is critical for the quantitative prediction of in vivo drug clearance and the magnitude of inhibitory drug interactions. A cause of inaccuracy in vitro arises from the assumption that all drug added to an incubation mixture is available for metabolism or inhibition. Many drugs bind non-specifically to the membrane of the in vitro enzyme source. The aims of this thesis were to: 1) investigate the comparative importance of lipophilicity (as log P), and pKa as determinants of the non-sp

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3

Schjølberg, Tiril Helgesen. "In Vitro Synthesis of Metabolites of three Anabolic Androgenic Steroids, by Human Liver Microsomes." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for bioteknologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-22910.

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Anabolic androgenic steroids are substances frequently misused to improve physicalperformance in sports. To reveal substances misused as doping, athlete urinesamples are collected and tested. To identify the steroid and/or its metabolitesin urine, reference compounds must exist for comparison. The time-consumingand ethical concerns about in vivo excretion studies for the examination of thesecompounds, make the use of liver fragment microsomes an attractive alternative.The aim of this thesis was to synthesize and identify metabolites from known andrare anabolic androgenic steroids, by the use o

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4

Maley, Mary. "The role of individual forms of cytochrome P450 in drug metabolism in human liver microsomes." Thesis, University of Aberdeen, 1996. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU078654.

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Human liver microsomal metabolism of nicardipine was investigated and compared to that of another dihydropyridine, felodipine, and to published results for other compounds belonging to this class of drugs. The metabolism of tamoxifen and two iododerivatives, idoxifene and 4-iodotamoxifen, were also investigated. Nicardipine metabolism by human liver microsomes was dissimilar to that of other dihydropyridines in several respects. For most dihydropyridines studied to date, conversion to the corresponding pyridine is the major metabolic pathway; the results from this study suggested that pyridine

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5

Abu-Omar, Ghada M. "Drug interactions and metabolism of cyclosporin A and steroids by human liver microsomes in vitro." Thesis, University of Aberdeen, 1992. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU545502.

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1) The purpose of this work is to study the enzymology of cyclosporin A (CsA) metabolism by human liver in vitro , in particular investigating the basis for interindividual variations and drug interactions involving CsA metabolism, and to apply this knowledge to the development of a non-invasive test for predicting an individual's ability to metabolise CsA in vivo . The ultimate aim is to help to improve CsA therapy by understanding the factors which determine its metabolism in patients. 2) Human liver microsomes metabolised cyclosporin A (Km 25M) to eight identifiable metabolites, which were

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6

Dowsley, Taylor Forbes. "CYP2E1-dependent bioactivation of 1,1-dichloroethylene to reactive intermediates in murine and human lung and liver microsomes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ38304.pdf.

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7

Strömqvist, Malin. "Development of quantitative methods for the determination of vemurafenib and its metabolites in human plasma." Thesis, Linköpings universitet, Kemi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-110076.

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Vemurafenib is a potent serine/threonine kinase inhibitor and is registered as Zelboraf® for the treatment of metastatic melanomas harboring BRAFV600E mutations. There is a large individual variation in drug response and the side effects observed among patients treated with Zelboraf® has proven to be severe. LC-MS/MS methods were developed to measure vemurafenib and its metabolites in human plasma for prediction of treatment outcome and side effects in order to individualize treatment with Zelboraf®. A novel, rapid quantification method was developed for vemurafenib using a stable isotope la

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8

Shepard, Dale Randall. "The Metabolism of Phenytoin by Human Liver Microsomes and Cytochrome P450s Expressed in Saccharomyces Cerevisiae and COS-1 Cells /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487931512618872.

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9

Uwimana, Eric. "Probing the PCB metabolome: metabolism of chiral and non-chiral polychlorinated biphenyls to chiral hydroxylated metabolites in humans and rats." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6657.

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Polychlorinated biphenyls (PCBs) continue to pose a health concern because of their predominance in the diet and air as well as in environmental samples and humans. PCB congeners with 3 or 4 chlorine substituents in ortho position have been associated with neurodevelopmental disorders. Hydroxylated metabolites (OH-PCBs) of these PCBs are also potentially toxic to the developing brain. Metabolism studies have mainly focused on animal models. However, preliminary data from this dissertation work have revealed PCB metabolism differences between laboratory animal models and humans in terms of meta

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10

Larabi, Islam Amine. "Nouveaux produits de synthèse : analyse, consommation et métabolisme ; Applications cliniques et médicolégales Rapid and simultaneous screening of new psychoactive substances and conventional drugs of abuse. A comparative study of Biochip Array Technology versus LC-MS/MS in whole blood and urine Development of a sensitive untargeted liquid chromatography– high resolution mass spectrometry screening devoted to hair analysis through a shared MS2 spectra database: A step toward early detection of new psychoactive substances Validation of an UPLC-MS/MS method for the determination of sixteen synthetic cannabinoids in human hair. Application to document chronic use of JWH-122 following a non-fatal overdose Development and validation of liquid chromatography-tandem mass spectrometry targeted screening of 16 fentanyl analogs and U-47700 in hair: Application to 137 authentic samples Prevalence and Surveillance of Synthetic Cathinones Use by Hair Analysis: An Update Review Prevalence of New Psychoactive Substances(NPS) and conventional drugs of abuse (DOA) in high risk populations from Paris(France) and its suburbs A cross sectional study by hair testing(2012–2017) Evaluation of drug abuse by hair analysis and self-reported use among MSM under PrEP: Results from a sub-study of the ANRS-IPERGAY trial. Hair testing for 3‑fluorofentanyl, furanylfentanyl, methoxyacetylfentanyl, carfentanil, acetylfentanyl and fentanyl by LC–MS/MS after unintentional overdose Drug‐facilitated sexual assault (DFSA) involving 4‐methylethcathinone (4‐MEC),3,4‐Methylenedioxypyrovalerone (MDPV), and doxylamine highlighted by hair analysis Metabolic Profiling of Deschloro-N-ethyl-ketamine (O-PCE) and identification of new target metabolites in urine and hair using human liver microsomes and high-resolution accurate mass spectrometry." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL029.

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L’objectif de ce travail a été de développer deux approches analytiques dédiées à l’analyse toxicologique des nouveaux produits de synthèse (NPS) dans différentes matrices biologiques (sang, urine et cheveux). La première est basée sur le criblage non ciblé par chimiluminescence sur biopuces et chromatographie liquide couplée à la spectrométrie de masse haute résolution (LC-HRMS) et la deuxième correspond à un criblage ciblé par spectrométrie de masse en tandem (LC-MS/MS). Ces deux approches ont ensuite été appliquées dans des études observationnelles pour évaluer la consommation de NPS dans d

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11

Kroetz, Deanna L. "Inhibition of human liver microsomal epoxide hydrolase /." Thesis, Connect to this title online; UW restricted, 1990. http://hdl.handle.net/1773/7958.

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12

Vollmar, Christian Verfasser], and Hans H. [Akademischer Betreuer] [Maurer. "New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone : studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine / Christian Vollmar. Betreuer: Hans H. Maurer." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2014. http://d-nb.info/1053725442/34.

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13

Habenschus, Maísa Daniela. "Estudos de inibição das enzimas do citocromo P450 pelo produto natural (-)-grandisina utilizando microssomas hepáticos de humanos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/59/59138/tde-06072016-095943/.

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A (-)- grandisina (GRA) é um produto natural da classe das lignanas e é encontrada em muitas espécies de plantas das regiões Norte e Nordeste do Brasil. Por apresentar diversas propriedades biológicas, como atividade tripanocida, anti-inflamatória, antinociceptiva, e principalmente atividade antileucêmica e antitumoral contra tumores de Ehrlich, a GRA pode ser considerada um potencial candidato a fármaco. Porém, para que a GRA se torne um fármaco são necessárias diversas etapas de estudos, incluindo estudos pré-clínicos de interações medicamentosas (DDI). As DDI ocorrem principalmente devido a

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14

Ameline, Alice. "Aspects analytiques, cliniques et médico-judiciaires des nouvelles substances psychoactives." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ018/document.

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En raison de la diffusion incontrôlée sur le e-commerce, la sécurité et l’alternative légale aux stupéfiants habituels, les nouvelles substances psychoactives (NPS), d’apparition récente (2008), sont au cœur des phénomènes récents d’addiction et de décès mal expliqués. Au-delà des différents défis dans nos sociétés (prévention, législation), la capacité d’identifier les NPS dans des échantillons biologiques pour caractériser leur utilisation, présente de nombreux challenges analytiques. L’objectif principal de cette thèse a été de collecter des échantillons biologiques (sang, urine, cheveux) p

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15

Al, Ali Ahmad. "Le dosage des cytochromes P450 (CYPs) humains par spectrométrie de masse : applications en toxicologie." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05P603/document.

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Les cytochromes P450 (CYPs) jouent un rôle essentiel dans le métabolisme oxydatif de nombreux composés endogènes et exogènes. L’expression de CYPs est extrêmement variable en fonction de facteurs physiopathologiques, génétiques et environnementaux. Le métabolisme des xénobiotiques par les CYPs dépend en partie de la nature, de la quantité et de l’activité d’isoformes des CYPs impliqués. L'analyse quantitative de l'expression de CYP dans les organes du métabolisme, tels que le foie, sont d'une importance particulière étant donné que la biotransformation réalisée par les CYPs est souvent un fact

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16

Tsai, I.-Lin, and 蔡易霖. "Identify the metabolites of methylone and ethylone using human liver microsomes and human urine." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/8b6k2p.

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碩士<br>國立臺灣大學<br>法醫學研究所<br>107<br>Synthetic cathinone is the most frequently abused new psychoactive substances (NPS) in Taiwan. Methylone and ethylone, which were categorized as scheduled III drug in 2012 and 2016 in Taiwan, are two derivatives of synthetic cathinone. It is important to investigate the metabolism of methylone and ethylone in order to find specific markers in human specimen. However, the metabolic profile of these two compounds are still limited especially for phase II metabolites. In previous study, methylone and ethylone each formed 7 metabolites through 5 metabolic pathways.

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17

McLure, James Alexander. "Physicochemical determinants of the non-specific binding of drugs to human liver microsomes." 2008. http://catalogue.flinders.edu.au/local/adt/public/adt-SFU20081102.165952/index.html.

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18

Madeira, Maria. "The effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6." Thesis, 2003. http://hdl.handle.net/2429/14177.

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Cimetidine is a liistamine H₂-receptor antagonist used in the treatment of peptic ulcer disorders. There have been numerous clinical observations of cimetidine drug-drug interactions, in some cases involving known substrates of cytochrome P450 (P450) 2D6. One explanation for these observations is impaired hepatic metabolism via inhibition o f P450s, the primary mediators of hepatic phase I metabolism of drugs. Cimetidine has been demonstrated to inhibit various P450 enzymes in vitro, including CYP2D6, but the inhibition constants are generally higher than the plasma concentrations measured fol

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19

Riley, Anna Ruth. "Propoxyphene, Norpropoxyphene, and Proadifen (SKF-525A) Are Mechanism Based Inhibitors of CYP3A4, CYP3A5, and CYP3A in Human Liver Microsomes." Thesis, 2008. http://hdl.handle.net/1805/1855.

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Indiana University-Purdue University Indianapolis (IUPUI)<br>The purpose of this study is to determine if propoxyphene and norpropoxyphene are mechanism-based (irreversible) inhibitors of CYP3A, and to determine if propoxyphene and norpropoxyphene are reversible inhibitors of CYP3A. Mechanismbased inhibition is a type of irreversible inhibition that results from an inhibitor or its metabolite binding to an enzyme during drug metabolism, which renders the enzyme nonfunctional. Propoxyphene is an analgesic that is frequently prescribed in the United States and Europe. It is metabolized by

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20

Hsun-Yi, Tseng, and 曾薰儀. "Study on Metabolism of Territrem A by Human Liver Microsomes and Human Cytochrome P450 3A4 expressed in V79 Chinese Hamster cells." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/81149866620663181463.

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碩士<br>國立臺灣大學<br>毒理學研究所<br>88<br>Abstract Territrem A (TRA) is a tremogenic mycotoxin isolated from the chloroform extracts of the sub-merged rice culture of Aspergillus terreus 23-1. The previous studies indicated that three metabolites, designated as MA1, MAX and MA2, were obtained when TRA was the substrate in liver microsomes of adult male Wistar rats which was pretreated with phenobarbital or dexamethasone. However, only MA1 was formed from TRA in liver microsomes of female rats. From chemical and immuno inhibition studies, we had suggested that CYP3A1/2 mainly involved in

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21

Liu, X., L. Hu, G. Ge, B. Yang, J. Ning, S. Sun, L. Yang, Klaus Pors, and J. Gu. "Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay." 2014. http://hdl.handle.net/10454/10502.

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No<br>Cytochrome P450 (CYP) is one of the most important drug-metabolizing enzyme families, which participates in the biotransformation of many endogenous and exogenous compounds. Quantitative analysis of CYP expression levels is important when studying the efficacy of new drug molecules and assessing drug-drug interactions in drug development. At present, chemical probe-based assay is the most widely used approach for the evaluation of CYP activity although there are cross-reactions between the isoforms with high sequence homologies. Therefore, quantification of each isozyme is highly desired

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22

Numa, Andres Masato. "The effect of Ginkgo Biloba extract on valproic acid metabolism by human liver microsomes from donors with the CYP2C9*1/*1 genotype." Thesis, 2005. http://hdl.handle.net/2429/17242.

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Ginkgo biloba extract (GBE) is a popular herbal preparation used primarily in the treatment of dementia, peripheral vascular diseases, and neurosensory problems. In this study, the effect of GBE on the oxidative metabolism of the anti-epileptic valproic acid (VPA) was investigated. Human liver microsomes (HLM) from donors with the CYP2C9*1/*1 genotype were incubated with VPA and GBE, and the formation of 4-ene-VPA, 4-OH-VPA, 5-OH-VPA, and 3-OH-VPA were monitored by GC/MS in NICI mode. GBE inhibited the formation of all four metabolites in a dose-dependent manner. GBE from three different

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23

Li, Yibai. "Pharmacogenetics of ketamine metabolism and immunopharmacology of ketamine." Thesis, 2014. http://hdl.handle.net/2440/106345.

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Ketamine is an anaesthetic agent that is being increasingly used at sub-anaesthetic doses as an analgesic or co-analgesic in the management of postoperative pain and chronic pain. In most countries, ketamine is administered as a racemic compound consisting of two enantiomers: (S)- and (R)-ketamine at a ratio of 1:1. Ketamine analgesia is frequently restricted by the low efficacy and large interindividual variability in drug response, which may be associated with the differences in the plasma pharmacokinetics. Previous in vitro studies suggested that ketamine is primarily cleared to its active

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24

Seibert, C., B. R. Davidson, B. J. Fuller, Laurence H. Patterson, W. J. Griffiths, and Y. Wang. "Multiple-approaches to the identification and quantification of cytochromes P450 in human liver tissue by mass spectrometry." 2009. http://hdl.handle.net/10454/6179.

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Here we report the identification and approximate quantification of cytochrome P450 (CYP) proteins in human liver microsomes as determined by nano-LC-MS/MS with application of the exponentially modified protein abundance index (emPAI) algorithm during database searching. Protocols based on 1D-gel protein separation and 2D-LC peptide separation gave comparable results. In total, 18 CYP isoforms were unambiguously identified based on unique peptide matches. Further, we have determined the absolute quantity of two CYP enzymes (2E1 and 1A2) in human liver microsomes using stable-isotope dilution m

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25

Sutherland, Mark H., Jason H. Gill, Paul M. Loadman, Jonathan P. Laye, Helen M. Sheldrake, Nicola A. Illingworth, Mohammed N. Alandas, et al. "Antitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder." 2012. http://hdl.handle.net/10454/6210.

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No<br>We identify cytochrome P450 1A1 (CYP1A1) as a target for tumor-selective drug development in bladder cancer and describe the characterization of ICT2700, designed to be metabolized from a prodrug to a potent cytotoxin selectively by CYP1A1. Elevated CYP1A1 expression was shown in human bladder cancer relative to normal human tissues. RT112 bladder cancer cells, endogenously expressing CYP1A1, were selectively chemosensitive to ICT2700, whereas EJ138 bladder cells that do not express CYP1A1 were significantly less responsive. Introduction of CYP1A1 into EJ138 cells resulted in 75-fold inc

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