Dissertations / Theses on the topic 'Cytochrome P450 3A'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 32 dissertations / theses for your research on the topic 'Cytochrome P450 3A.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
Givens, Raymond Carlos Maeda Nobuyo. "Physiologic effects of cytochrome P450 3A activity." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1371.
Full textTitle from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Nutrition, School of Public Health." Discipline: Nutrition; Department/School: Public Health.
Westlind, Johnsson Anna. "Pharmacogenetics of human cytochrome P450 3A (CYP3A) enzymes /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-688-x.
Full textJohnson, Trevor Nigel. "Developmental and pathological changes in intestinal cytochrome P450 3A." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.482841.
Full textTydén, Eva. "Cytochrome P450 3A and ABC-transport proteins in horse /." Uppsala : Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2008. http://epsilon.slu.se/200893.pdf.
Full textCuri, Pedrosa Rozangela. "Effet de quelques anti-secrétoires gastriques sur l'expression des cytochromes P450 1A et 3A hépatiques humains : implication des cytochromes P450 3A dans le métabolisme de l'omeprazole." Montpellier 1, 1992. http://www.theses.fr/1992MON13519.
Full textEngman, Helena. "Intestinal barriers to oral drug absorption : cytochrome P450 3A and ABC-transport proteins /." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3599.
Full textMugundu, Ganesh. "Pharmacogenetic Impact on Metabolism and Cytochrome P450 (CYP)3A Inductive Effect of Tamoxifen." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1266596002.
Full textZerilli, Alain. "Cytochromes P450 2E1 et 3A : spécificité de l'induction tissulaire chez le rat, spécificité des substrats du P450 2E1." Brest, 1997. http://www.theses.fr/1997BRES3102.
Full textSwales, Karen Elizabeth. "An investigation of host cell effects on the xenobiotic induction of cytochrome P450 3A." Thesis, University of Surrey, 2002. http://epubs.surrey.ac.uk/843184/.
Full textSalphati, Laurent. "P-glycoproteine et cytochrome p450 3a : interactions potentielles et roles complementaires dans l'absorption et la disposition des drogues." Paris 11, 1998. http://www.theses.fr/1998PA114805.
Full textSachdeva, Karuna. "Regulation of cytochrome P450-3A (CYP3A) and pregnane X receptor (PXR) : implications to drug-drug interactions /." View online ; access limited to URI, 2005. http://0-wwwlib.umi.com.helin.uri.edu/dissertations/dlnow/3186919.
Full textLE, BRICQUIR YANN. "Effet de l'interferon alpha sur les cytochromes p-450 1a2 et 3a chez les malades atteints d'hepatite chronique virale c." Montpellier 1, 1993. http://www.theses.fr/1993MON11150.
Full textNALLANI, CHAKRAVARTHULA SRIKANTH. "DIFFERENTIAL INDUCTION OF HEPATIC CYTOCHROME P450 3A ENZYMES(S) BY TAXANE ANTICANCER AGENTS: MOLECULAR MECHANISMS AND CLINICAL IMPLICATIONS." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1022623309.
Full textFakhoury, May. "Pharmacogénétique en pédiatrie : 1-Expression du complexe CYP3A/P-gp dans l'entérocyte humain : 2-Implications des polymorphismes pharmacogénétiques dans la prise en charge des leucémies aiguës lymphoblastiques." Paris 5, 2005. http://www.theses.fr/2005PA05P625.
Full textXenobiotic disposition in the organism is highly variable among individuals and due to the impact of age and pharmacogenetic polymorphisms. A- Fundamental pharmacology project concerning the expression of CYP3A/P-gp complex in the human duodenum : - throughout post-natal development (localization and mRNA expression) - during systemic inflammation (Crohn's disease). Clinical pharmacology and pharmacogenetic project in children with acute lymphoblastic leukemia (LAL) : - evaluation of the variability in thiopurine S-methyltransferase (TPMT) during maintenance therapy - estimation of the pharmacokinetic parameters of methotrexate (MTX) and the proposal of a limited sampling strategy (H24 and H48) - impact of genetic polymorphisms (metabolic enzymes and transport proteins of anti-neoplasic agents) on the occurrence of side effects: preliminary results of two hospitals, Robert Debré (France) and Hôtel-Dieu de France (Beirut)
Drocourt, Lionel. "Régulation de l'expression des cytochromes P450 des sous-familles 2B, 2C et 3A dans l'hépatocyte humain : rôles physiologiques et pharmacologiques des récepteurs nucléaires GR, PXR, et VDR." Montpellier 2, 2001. http://www.theses.fr/2001MON20203.
Full textMatsubayashi, Keiko. "Contribution of cytochrome P450 3A pathway to bromocriptine metabolism and effects of ferrous iron and hypoxia-reoxygenation on its elimination in the perfused rat liver." Kyoto University, 1997. http://hdl.handle.net/2433/202219.
Full textCOSTET, PHILIPPE. "Utilisation des techniques de transgenese : analyse du phenotype murin deficient en recepteur nucleaire pparalpha et elaboration d'une lignee murine transgenique de surexpression du cytochrome p450 3a bovin." Toulouse 3, 1999. http://www.theses.fr/1999TOU30016.
Full textCavelier, Adeline. "Complementarité des protéines de detoxication et trafic intracellulaire." Phd thesis, Université René Descartes - Paris V, 2007. http://tel.archives-ouvertes.fr/tel-00553511.
Full textBorn, Stephanie Lynn 1968. "Characterization of canine cytochromes P450 2B and 3A." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290587.
Full textSamer, Caroline F. "Impact des cytochromes P450 2D6 et 3A sur les paramètres pharmacocinétiques et pharmacodynamiques de l'oxycodone /." Genève : Ed. Médecine et hygiène, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253454.
Full textDenk, Annette. "Der Effekt von Ursodeoxycholsäure auf den Cytochrom P450 3A-Metabolismus bei primär biliärer Zirrhose und gesunden Probanden." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-44811.
Full text"Physiologic effects of cytochrome P450 3A activity." THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL, 2008. http://pqdtopen.proquest.com/#viewpdf?dispub=3289052.
Full textLee, Su-Jun. "Cytochrome P450 3A forms in rainbow trout (Oncorhynchus mykiss)." Thesis, 2001. http://hdl.handle.net/1957/33090.
Full textWonganan, Piyanuch. "A mechanistic study of how adenovirus infection alters the expression and function of hepatic cytochrome P450 3A." Thesis, 2010. http://hdl.handle.net/2152/ETD-UT-2010-08-1969.
Full texttext
"Assessment of cytochrome P450 3A activity and relationship to response to statin therapy." 2013. http://library.cuhk.edu.hk/record=b5884361.
Full textThesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 156-190).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Jian, Wen-Chi, and 簡文琪. "Gender-and Age-Related Changes in Territrems Metabolism by Cytochrome P450 3A family in Rat Liver Microsomes." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/37733821266465215242.
Full text國立臺灣大學
毒理學研究所
91
Three tremogenic mycotoxines, designated as territrem A, B and C (TRA, TRB and TRC) were isolated from a chloroform extract of rice culture of Aspergillus terreus 23-1.The metabolism of TRA in liver microsomes of adult male and female rats have been studied. Three metabolites of TRA were formed by three sequential oxidative steps in male rats. There are first, hydroxylation at the 4b-C methyl group of TRA to form MA1; second, oxidation at 4b-C hydroxyl group of MA1 to form MAX; and third, decarbonylation at the 4b-C oxo group of MAX to form MA2. However, in female only MA1 was formed from TRA. Further, studies of cytochrome P450 isforms catalyzing TRA metabolism revealed that MA1 formation is catalyzed by both CYP3A1 and CYP3A2, while the formation of MAX and MA2 are catalyzed by CYP3A2. The sex difference of both amounts of protein and mRNA of CYP3A1/2 expression and territrems metabolism were examined in the present study. Many studies concerning age-related changes in CYP450 linked to metabolism of xenobiotics and drug have been reported. Therefore, next study of CYP3A1 and CYP3A2 related to age and sex hormone are our major concern. In the present studies, the following results were obtained: (1)Both protein and mRNA of CYP3A1 are constitutively expressed in both gender at 2- to 76-week-old age. (2)The protein levels and mRNA of CYP3A2 constitutively expressed in 2- to 52-week-old male rats, but they decreased after 76-week-old age, and decreased in female rat when after 6-week-old. (3)The expression of CYP3A1 or CYP3A2 in male rats are generally higher than female rats. (4)Formation of the different metabolites was due to change of aromatic moiety of territrems. (5)Formation of MAX and MA2 decreased after 52-week-old male rats and ceased after 6-week-old female rats. (6)The amount of MB2 formed in female rats was less than in male rats, but the amount of MB1 (TRC metabolites) formed in female rats was higher than male rats. (7)The protein levels of CYP3A2, production of MAX and MA2 were restored by administration on high dose testosterone (750 mg) in the castrated male rats. Therefore, it is concluded that: (1) The metabolism of TRA have sexual difference were related to the protein and mRNA expression of CYP3A2. The different metabolites formed could be due to the modification of the chemical structure of the aromatic moiety of territrems. The protein levels and mRNA expression of CYP3A2 and efficiency of territrems metabolism were decreased after 76-week-old that cause feminization at elder age of male rats. (2)Testosterone status modulated CYP3A2 expression and caused sex differenced of metabolism. For instances, serum level of testosterone decreased after aging and then changed territrems metabolism efficiency. In conclusion, age- and gender-related changes on territrems metabolism were due to CYP3A2 expression which regulated by testosterone.
Lin, Yu-Hsuan, та 林侑璇. "1.Inhibition Study of Territrem 4β-C hydroxylation and O-demethylation by Seven Human Cytochrome P450 3A4 substrates;2.Application of the Relative Activity Factor to Approach the Role of Cytochrome P450 3A to the Metabolism of Territrems by Wistar Rats a". Thesis, 2007. http://ndltd.ncl.edu.tw/handle/16537366566039898879.
Full text國立臺灣大學
毒理學研究所
95
1. Inhibition Study of Territrem 4β-C hydroxylation and O-demethylation by Seven Human Cytochrome P450 3A4 substrates Territrems are the structure related tremogenic mycotoxins, which are produced by Aspergillus terreus 23-1. Previous research indicated that MA1 can be produced from TRA hydroxylation, and TRB can produce MB2 and MB4 by 4β-C hydroxylation and O-demethylation. These reactions are mainly catalyzed by P450 3A4 in liver. Structure of CYP3A4 contains great active site, and also capable of binding of more than two substrates. Interactions between substrates cause the kinetics of CYP3A4 become atypical. In addition, some amino acids in CYP3A4 active site plays an important role in substrate binding. To understand the relations of the location of TRA and TRB metabolism, this experience uses cell line V79MZh3A4 which expressing human CYP3A4. We provide TRA and TRB in time to metabolize and analyze the metabolite by HPLC. Double reciprocal plot facilitates understanding of types of inhibition. Results shows that in the process of TRA producing MA1 and TRB producing MB2, TRB and TRA are mutually mixed-type inhibition. In the process of TRB producing MB4, TRB and TRA are un-competitive inhibition. To delve more into the combinational location of TRB on CYP3A4, select seven kinds of CYP3A4 substrates to metabolize with TRB at the same time, in order to indirectly infer the location of TRB on CYP3A4. The results presents that in the metabolizing process from TRB to MB2, inhibition occurs with testosterone and un-inhibition occurs with budesonide. Also, in the metabolizing process of TRB to MB4, un-competitive inhibition occurs with testosterone, etoposide and mixed-type inhibition occurs with budesonide. Inferring from above, combination of TRA and TRB on CYP3A4 have different location, but one combination of another might change the structural location, causing declines affinity of CYP3A4. Additionally, by predicting the competitive locations of TRB and testosterone, we suggest that TRB can form a hydrogen bond with serine-119 in CYP 3A4 active site. But above inhibitors locate differently, and they only interact with each other. About the modes of TRB and substrate, it still remains unknown. Moreover, our experiment observed many atypical characteristics of CYP3A4, proving the complexity of CYP3A4. 2.Application of the Relative Activity Factor to Approach the Role of Cytochrome P450 3A to the Metabolism of Territrems by Wistar Rats and Human Liver Microsomes Cytochrome P450 is the most crucial oxidative enzyme system responsible for metabolizing over 90% endogenous and xenobiotics in human. Its prevalent characteristics of substrate specificity often result in interactions between substrates and, moreover, two or more CYP enzymes often contribute to the metabolism of a single drug. Due to above reasons, it’s important to determine the relative contribution of each CYP to net metabolism of the drug.. The concept of RAF (relative activity factor) was first proposed by Crespi at 1995. The RAF approach has been applied successfully to estimate CYP isoforms contribution to drug metabolism. According to the previous research in our Laboratory, during metabolism of TRB to MB2, CYP3A4 was major involving enzyme, containing 97.1%: during metabolism of TRB to MB4, CYP3A4 was the major, containing 64.3%. To clarify further the relative contributions of each CYP isoforms to the metabolism of TRA and TRB, we use rP450s and different ages and genders of human, and Wistar rats, and calculate the RAF. Experiment results indicated that during metabolism of TRA to MA1 in rat and human liver microsomes, CYP3A2 (84.7%) and CYP3A4 (85.9%) are major involving enzyme. During metabolism of TRB to MB2 and MB4 in rat liver microsomes, CYP3A1 (92%) and CYP3A2 (65.2%) are major involving enzyme. Furthermore, the results indicated that comparing the sex and age differences, 8-week-old male rats presented best results in the process of metabolism. But for human bodies, there is no obvious correlation between age and sex. Many factors might explain this, including the chemical structure of TRA and TRB, the mRNA and protein expression level of CYP3A1/2 in rats, the expression level and activity of CYP3A4/5 in different human bodies, amino acid sequence homology between CYP3A1/2 and CYP3A4/5, and the substrate binding sites in CYPs.
Jelínková, Sandra. "Vliv vandetanibu, lenvatinibu a ellipticinu na expresi potkaních cytochromů P450 1A a 3A." Master's thesis, 2018. http://www.nusl.cz/ntk/nusl-379348.
Full textSvobodová, Lucie. "Oxidace protinádorového léčiva ellipticinu cytochromy P450 3A a 2B." Master's thesis, 2007. http://www.nusl.cz/ntk/nusl-374387.
Full textChen, Pei-Chun, and 陳佩君. "The role of cytochrome P450 3A in the metabolism of Territrem B and C in Liver microsomes from 14-week-old Wistar rats;The effect of sex hormone and xenobiotics on CYP450 3A1/2 expression in rat hepatoma cells McA-RH8994 and McA-RH7777." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/27384862665791448128.
Full text國立臺灣大學
毒理學研究所
92
第一章 Territrem is a tremogenic mycotoxin isolated from the chloroform extracts of rice culture of Aspergillus terreus 23-1. The previous study showed that three metabolites MA1, MAX and MA2 of territrem A (TRA) were formed in male rats, and gender difference in TRA metabolism of Wistar rats from that only MA1 formation was formed in female rats. Further study of cytochrome P450 involvement TRA metabolism suggested CYP3A1 is mainly responsible for MA1 formation and CYP3A2 is responsible for MA1, MAX, and MA2 formation. It has been reported that four metabolites of territrem B (TRB), designated as MB1, MB2, MB3, and MB4 and one metabolite of territrm C (TRC), designated as MB1, were formed from liver microsomes of both sexs Wistar rats. The metabolism of TRB and TRC related to gender difference and CYP450 family involved were not investigated. To investigate which cytochrome P450 isoforms were involved in TRB and TRC metabolism, four CYP450 isoform-specific inhibitors ( furafylline, orphenadrine, cimetidine, and troleandomycin) and antibodies against CYP1A2, CYP2B1, CYP2C11, or CYP3A2 were used. The gender difference in TRB and TRC metabolism in liver microsomes of 14-week-old male and female Wistar rats were also investigated. The following results indicated that (1) Metabolism of TRB to MB2, and metabolism of TRC to MB1 were observed in both sexes. The amounts of MB2, MB4, and MB1 formed were higher in male rats.(2) Formation of MB2, MB4, and MB1 was markedly inhibited by cimetidine and troleandomycin, but less by furafylline and orphenadrine. (3) Anti-CYP3A2 antibody markedly inhibited MB2, MB4, and MB1 formation, while antibodies against CYP1A1, CYP2B1, or CYP2C11 had little effect, and (4) Of the seven tested supersomes from baculovirus-transformed insect cells expressing rat CYP450 isoforms ( 1A1, 1A2, 2B1, 2C11, 2C12, 3A1, and 3A2), only those expressing CYP3A1 and CYP3A2 metabolized TRB and TRC. (5) The amounts of MB2, MB4, and MB1 were related to the 6��-testosterone hydroxylase activity and CYP3A1/2 protein content. (6) Immunoblotting showed that CYP3A1 was expressed in both sexes, but at different levels, while CYP3A2 was only expressed in male. These results suggest that the formation of MB2, MB4, and MB1 in liver microsomes from 14-week-old rats of either sex is mediated by CYP3A1 and CYP3A2. 第二章 Cytochrome P450s constitute a multigene family of hemoproteins responsible for the metabolism of numerous xenobiotics, including therapeutic drugs, environmental chemicals, and dietary constituents, as well as such endogenous compounds as steroid and bile acids. Among them, CYP3A enzymes are the most abundant P450 enzymes and involved two thirds of xenobiotics. In the rat exists as two isoenzymes, CYP3A1 and CYP3A2. The protein level of CYP3A2 was expressed in 20-day-old rat of both genders, constitutively expressed in male rats, but decreased after puberty in female rats and extinguished in the adult female. Previous studies showed that (1) the sex difference in TRA metabolism was observed. (2) CYP3A1 and CYP3A2 are mainly responsible for TRA metabolism. (3) Treatment of Wistar rats with either dexamethasone (DEX) or Phenobarbital (PB) markedly increased in CTP3A protein level . Whereas, a similar rise in the metabolism of TRA. (4) In the gonadectomized male rats, MAX and MA2 formation were reversed when the animals were further treated by testosterone. Whereas, CYP3A2 protein levels was reversed by further testosterone treatment with gonadectomized male rats. Therefore it suggested that testosterone may regulate CYP3A2 gene expression. For this purpose, two cultured cell lines, called McA-RH8994 and McA-RH7777, were established from rat hepatoma cells by in vitro culture with cytochrome P450 inducer, such as DEX and PB, and sex hormone, such as dihydrotestosterone (DHT) and ���{estradiol investigated protein levels, mRNA, and transcription factors responsible for CYP3A1 and CYP3A2. Whereas, it was also investigated 6��-testosterone hydroxylase activity and the metabolism of TRA in these two cell lines.. In the present study, the following results were obtained : (1) CYP3A1 mRNA and protein level are increased by DEX and PB 72 hr treatment. (2) Only MA1 formed from TRA by DEX treatmentthe. (3) 6β-hydroxytestosterone formation was higher in DEX and PB treatment. (4) For nuclear transcription factor of CYP3A, PXR/RXR�� mRNA and protein level are increased by DEX treatment, the protein level of glucocorticoid receptor (GR) was markedly decreased, and the protein levels of androgen receptor (AR) was not changed. These results suggest that (1) In vitro cell culture, CYP3A1 was markedly induced by xenobiotics, while endogenous, such as sex hormone, may be indirectly regulated CYP3A2 gene expression. (2) DEX induce CYP3A1 level through PXR/RXR?rather than protypical GR pathway.
Fenneteau, Frédérique. "Prédiction des impacts pharmacocinétiques des interactions médicamenteuses impliquant des CYP3A et les glycoprotéines-P : développement de modèles physiologiques et analyse de sensibilité." Thèse, 2009. http://hdl.handle.net/1866/3563.
Full textEarly knowledge of pharmacokinetic properties of a new drug candidate and good characterization of the impact of drug-drug interaction (DDI) on those properties is of crucial importance in the process of drug research and development. The main objective of this thesis consisted in the conception of PBPK models able to predict the drug disposition in the absence and presence of metabolic and transport activity modulation. The first part of this work aimed to develop a PBPK model that incorporates the efflux function of P-gp expressed in various tissues, in order to predict the impact of P-gp activity modulation on drug distribution. This approach, based on in vivo-in vitro extrapolation for estimating the transport-related parameters, allowed the prediction of domperidone distribution in heart and brain of wild-type mice and P-gp deficient mice. The model pointed out the protective function of P-gp in brain whereas it showed the negligible protective effect of P-gp in heart. The second part of the project aimed to perform the global sensitivity analysis of the previous PBPK model, in order to investigate how the uncertainly and variability of the correlated physiological parameters influence the outcome of the drug distribution process. While a moderate variability of the model predictions was observed, this analysis confirmed the importance for a better quantitative characterization of parameters related to the transport processes trough the blood-tissue membrane. Accounting for the input correlation allowed the delineation of the true contribution of each input to the variability of the model outcome. The last part of the project consisted in predicting the pharmacokinetics of selected CYP3A substrates administered at a single oral dose to human, alone or with an inhibitor. Successful predictions were obtained for a single administration of the CYP3A substrates. Some deviations were observed between the predictions and in vivo plasma profiles in the presence of DDI. However, the impact of inhibition on the PK parameters of the selected substrates and the impact of grapefruit juice-mediated inhibition on the extent of intestinal pre-systemic elimination were predicted within a very acceptable error range. Overall, this thesis demonstrated the ability of PBPK models to predict DDI with promising accuracy.
Denk, Annette Carola [Verfasser]. "Der Effekt von Ursodeoxycholsäure auf den Cytochrom-P450-3A-Metabolismus bei primär biliärer Zirrhose und gesunden Probanden / vorgelegt von Annette Carola Denk." 2005. http://d-nb.info/977662837/34.
Full text