Relevant bibliographies by topics / CYP3A4

Academic literature on the topic 'CYP3A4'

Author: Grafiati
Published: 4 June 2021
Last updated: 19 February 2022

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Journal articles on the topic "CYP3A4"

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Sun, Jie-Yu, Ze-Jun Xu, Fang Sun, Hui-Lei Guo, Xuan-Sheng Ding, Feng Chen, and Jing Xu. "Individualized Tacrolimus Therapy for Pediatric Nephrotic Syndrome: Considerations for Ontogeny and Pharmacogenetics of CYP3A." Current Pharmaceutical Design 24, no. 24 (November 8, 2018): 2765–73. http://dx.doi.org/10.2174/1381612824666180829101836.

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Tacrolimus is used initially as an immunosuppressant drug in solid organ transplant population. This calcineurin inhibitor has also been recommended by KDIGO Clinical Practice Guideline for Glomerulonephritis for the treatment of nephrotic syndrome in children and adults. Tacrolimus is characterized by a narrow therapeutic index and large pharmacokinetic (PK) variations. Therefore, routine Therapeutic Drug Monitoring (TDM) is critical to keep tacrolimus blood levels within the therapeutic range. Tacrolimus is mainly metabolized by cytochrome P450 (CYP) enzymes 3A5 and 3A4. Actually, for pediatric patients, they are totally different to adults. Profound changes in CYP3A expression and activity occur throughout fetal life and in the neonatal and childhood periods thereby influencing their catalytic function. CYP3A7, CYP3A5, and CYP3A4 display an age-dependent maturation pattern. Notably, the CYP3A7-CYP3A4 switch taking place during the very early life will affect tacrolimus metabolism. Meanwhile, CYP3A isoforms are polymorphic enzymes, especially for CYP3A5. The guideline has recommended that the tacrolimus dosage should be adjusted according to the CYP3A5 genotype. Additionally, genetic CYP3A4 variation (e.g., CYP3A4*22) is also associated with interindividual variability of exposure level to tacrolimus. However, age (ontogeny) sometimes trumps genetics (genotype) in determining the enzymatic functions (phenotype) in pediatric patients. It’s important to discriminate at what age the ontogeny plays key roles and at what age genetic variation become a major determinant. Thus, we need to better understand the mechanisms driving the CYP3A maturation and integrate ontogeny and genetics into the tacrolimus disposition, thereby tailoring the dosage individually for pediatric NS patients at different developmental stages.
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Niwa, Toshiro, Kanae Narita, Ayaka Okamoto, Norie Murayama, and Hiroshi Yamazaki. "Comparison of Steroid Hormone Hydroxylations by and Docking to Human Cytochromes P450 3A4 and 3A5." Journal of Pharmacy & Pharmaceutical Sciences 22 (July 24, 2019): 332–39. http://dx.doi.org/10.18433/jpps30558.

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Purpose: Hydroxylation activity at the 6β-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (P450 or CYP) 3A4 and CYP3A5 and their molecular docking energy values were compared to understand the catalytic properties of the major forms of human CYP3A, namely, CYP3A4 and CYP3A5. Methods: Testosterone, progesterone, and cortisol 6β-hydroxylation activities of recombinant CYP3A4 and CYP3A5 were determined by liquid chromatography. Docking simulations of these substrates to the heme moiety of reported crystal structures of CYP3A4 (Protein Data Bank code ITQN) and CYP3A5 (6MJM) were conducted. Results: Michaelis constants (Km) for CYP3A5-mediated 6β-hydroxylation of testosterone and progesterone were approximately twice those for CYP3A4, whereas the value for cortisol 6β-hydroxylation mediated by CYP3A5 was similar to the value for that by CYP3A4. Maximal velocities (Vmax) of the three steroid hormones 6β-hydroxylation catalyzed by CYP3A5 were 30%-63% of those by CYP3A4. Thus, Vmax/ Km values of these hormones for CYP3A5 resulted in 22%-31% of those for CYP3A4. The differences in the docking energies between CYP3A4 and CYP3A5 for steroid hormones were slightly correlated to the logarithm of CYP3A5/CYP3A4 ratios for Km values (substrate affinity). Conclusions: The Vmax, rather than Km values, for CYP3A5-mediated 6β-hydroxylation of three steroid hormones were different from those for CYP3A4. Molecular docking simulations could partially explain the differences in the accessibility of substrates to the heme moiety of human CYP3A molecules, resulting in the enzymatic affinity of CYP3A4 and CYP3A5.
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Kamdem, Landry K., Frank Streit, Ulrich M. Zanger, Jürgen Brockmöller, Michael Oellerich, Victor W. Armstrong, and Leszek Wojnowski. "Contribution of CYP3A5 to the in Vitro Hepatic Clearance of Tacrolimus." Clinical Chemistry 51, no. 8 (August 1, 2005): 1374–81. http://dx.doi.org/10.1373/clinchem.2005.050047.

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Abstract Background: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these organs, require higher doses of tacrolimus, but the exact mechanism of this association is unknown. Methods: cDNA-expressed CYP3A enzymes and a bank of human liver microsomes with known CYP3A4 and CYP3A5 content were used to investigate the contribution of CYP3A5 to the metabolism of tacrolimus to 13-O-demethyltacrolimus as quantified by liquid chromatography–tandem mass spectrometry. Results: Demethylation of tacrolimus to 13-O-demethyltacrolimus was the predominant clearance reaction. Calculated Km and Vmax values for CYP3A4, CYP3A5, and CYP3A7 cDNA-expressed microsomes were 1.5 μmol/L and 0.72 pmol · (pmol P450)−1 · min−1, 1.4 μmol/L and 1.1 pmol · (pmol P450)−1 · min−1, and 6 μmol/L and 0.084 pmol · (pmol P450)−1 · min−1, respectively. Recombinant CYP3A5 metabolized tacrolimus with a catalytic efficiency (Vmax/Km) that was 64% higher than that of CYP3A4. The contribution of CYP3A5 to 13-O-demethylation of tacrolimus in human liver microsomes varied from 1.5% to 40% (median, 18.8%). There was an inverse association between the contribution of CYP3A5 to 13-O-demethylation and the amount of 3A4 protein (r = 0.90; P <0.0001). Mean 13-O-demethylation clearances in CYP3A5 high and low expressers, estimated by the parallel-tube liver model, were 8.6 and 3.57 mL · min−1 · (kg of body weight)−1, respectively (P = 0.0088). Conclusions: CYP3A5 affects metabolism of tacrolimus, thus explaining the association between CYP3A5 genotype and tacrolimus dosage. The importance of CYP3A5 status for tacrolimus clearance is also dependent on the concomitant CYP3A4 activity.
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Maruf, AA, MU Ahmed, M. A. K. Azad, M. Ahmed, and A. Hasnat. "CYP3A Genotypes in Bangladeshi Tuberculosis Patients." Bangladesh Medical Research Council Bulletin 38, no. 1 (April 22, 2012): 1–5. http://dx.doi.org/10.3329/bmrcb.v38i1.6978.

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The purpose of this study is to investigate the genotype and allelic frequencies of CYP3A in Bangladeshi Tuberculosis (TB) patients which may help for individualized drug dosing and improved therapeutics. Genotyping was done using the extracted genomic DNA from 90 TB patients followed by amplification of target alleles by PCR. Amplified alleles were then digested by restriction enzymes followed by gel electrophoresis & sequencing to identify the targeted alleles namely CYP3A4*1B, CYP3A4*2, CYP3A4*4, CY3A4*5, CYP3A4*6, CYP3A4*10, CYP3A4*18, and CYP3A5*3. In TB patients, no samples were positive for CYP3A4*2, CYP3A4*4, CYP3A4*5, CYP3A4*6, CYP3A4*10, and CYP3A4*18 alleles. One sample was found to be heterozygous for CYP3A4*1B (1.11%). The wild homozygous (CYP3A5*1/*1) genotype frequency was 7.78%, the heterozygous (CYP3A5*1/*3) frequency was 42.22% and the homozygous mutant (CYP3A5*3/*3) frequency was 50% in Bangladeshi TB patients. The absence of the common polymorphic gene suggests that there will be no impact of CYP3A drug metabolizing enzymes on antituberculosis drugs.DOI: http://dx.doi.org/10.3329/bmrcb.v38i1.6978Bangladesh Med Res Counc Bull 2012; 38: 1-5
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Klees, Theresa Mariero, Pamela Sheffels, Kenneth E. Thummel, and Evan D. Kharasch. "Pharmacogenetic Determinants of Human Liver Microsomal Alfentanil Metabolism and the Role of Cytochrome P450 3A5." Anesthesiology 102, no. 3 (March 1, 2005): 550–56. http://dx.doi.org/10.1097/00000542-200503000-00012.

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Background There is considerable unexplained interindividual variability in the clearance of alfentanil. Alfentanil undergoes extensive metabolism by cytochrome P4503A4 (CYP3A4). CYP3A5 is structurally similar to CYP3A4 and metabolizes most CYP3A4 substrates but is polymorphically expressed. Livers with the CYP3A5*1 allele contain higher amounts of the native CYP3A5 protein than livers homozygous for the mutant CYP3A5*3 allele. This investigation tested the hypothesis that alfentanil is a substrate for CYP3A5 and that CYP3A5 pharmacogenetic variability influences human liver alfentanil metabolism. Methods Alfentanil metabolism to noralfentanil and N-phenylpropionamide was determined in microsomes from two groups of human livers, characterized for CYP3A4 and CYP3A5 protein content: low CYP3A5 (2.0-5.2% of total CYP3A, n = 10) and high CYP3A5 (46-76% of total CYP3A, n = 10). Mean CYP3A4 content was the same in both groups. The effects of the CYP3A inhibitors troleandomycin and ketoconazole, the latter being more potent toward CYP3A4, on alfentanil metabolism were also determined. Results In the low versus high CYP3A5 livers, respectively, noralfentanil formation was 77 +/- 31 versus 255 +/- 170 pmol . min . mg, N-phenylpropionamide formation was 8.0 +/- 3.1 versus 20.5 +/- 14.0 pmol . min . mg, and the metabolite ratio was 9.5 +/- 0.4 versus 12.7 +/- 1.4 (P < 0.05 for all). There was a poor correlation between alfentanil metabolism and CYP3A4 content but an excellent correlation when CYP3A5 (i.e., total CYP3A content) was considered (r = 0.81, P < 0.0001). Troleandomycin inhibited alfentanil metabolism similarly in the low and high CYP3A5 livers; ketoconazole inhibition was less in the high CYP3A5 livers. Conclusion In microsomes from human livers expressing the CYP3A5*1 allele and containing higher amounts of CYP3A5 protein, compared with those with the CYP3A5*3 allele and little CYP3A5, there was greater alfentanil metabolism, metabolite ratios more closely resembled those for expressed CYP3A5, and inhibitors with differing CYP3A4 and CYP3A5 selectivities had effects resembling those for expressed CYP3A5. Therefore, alfentanil is metabolized by human liver microsomal CYP3A5 in addition to CYP3A4, and pharmacogenetic variability in CYP3A5 expression significantly influences human liver alfentanil metabolism in vitro. Further investigation is warranted to assess whether the CYP3A5 polymorphism is a factor in the interindividual variability of alfentanil metabolism and clearance in vivo.
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Leskelä, S., E. Honrado, C. Montero-Conde, I. Landa, A. Cascón, R. Letón, P. Talavera, et al. "Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer." Endocrine-Related Cancer 14, no. 3 (September 2007): 645–54. http://dx.doi.org/10.1677/erc-07-0078.

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Testosterone is essential for the growth and function of the luminal prostate cells, but it is also critical for the development of prostate cancer, which in the majority of the cases derives from luminal cells. Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. However, it is unknown whether the CYP3A enzymes are expressed at relevant levels in the prostate and which polymorphisms could affect this tissue-specific CYP3A activity. Thus, we measured CYP3A4, CYP3A5, CYP3A7, and CYP3A43 mRNA in 14 benign prostatic hyperplasias and ten matched non-tumoral/tumoral prostate samples. We found that CYP3A5 mRNA in non-tumoral prostate tissue was 10% of the average amount of liver samples, whereas the expression of the other CYP3A genes was much lower. Similarly to liver, CYP3A5*3 polymorphism decreased CYP3A5 mRNA content 13-fold. CYP3A5 protein was detected in non-tumoral prostate microsomes by western blot, and immunohistochemistry (IHC) localized CYP3A5 exclusively in the basolateral prostate cells. In contrast to the normal tissue, IHC and RT-PCR showed that tumoral tissue lacked CYP3A5 expression. In conclusion, prostate basolateral cells express high levels of CYP3A5 which dramatically decrease in tumoral tissue. This finding supports an endogenous function of CYP3A5 related to the metabolism of intra-prostatic androgens and cell growth, and that polymorphisms affecting CYP3A5 activity may result in altered prostate cancer risk and aggressiveness.
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Raymond, Lendelle, Nikita Rayani, Grace Polson, Kylie Sikorski, Ailin Lian, and Melissa A. VanAlstine-Parris. "Determining the IC50 Values for Vorozole and Letrozole, on a Series of Human Liver Cytochrome P450s, to Help Determine the Binding Site of Vorozole in the Liver." Enzyme Research 2015 (November 9, 2015): 1–4. http://dx.doi.org/10.1155/2015/321820.

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Vorozole and letrozole are third-generation aromatase (cytochrome P450 19A1) inhibitors. [11C]-Vorozole can be used as a radiotracer for aromatase in living animals but when administered by IV, it collects in the liver. Pretreatment with letrozole does not affect the binding of vorozole in the liver. In search of finding the protein responsible for the accumulation of vorozole in the liver, fluorometric high-throughput screening assays were used to test the inhibitory capability of vorozole and letrozole on a series of liver cytochrome P450s (CYP1A1, CYP1A2, CYP2A6, and CYP3A4). It was determined that vorozole is a potent inhibitor of CYP1A1 (IC50 = 0.469 μM) and a moderate inhibitor of CYP2A6 and CYP3A4 (IC50 = 24.4 and 98.1 μM, resp.). Letrozole is only a moderate inhibitor of CYP1A1 and CYP2A6 (IC50 = 69.8 and 106 μM) and a very weak inhibitor of CYP3A4 (<10% inhibition at 1 mM). Since CYP3A4 makes up the majority of the CYP content found in the human liver, and vorozole inhibits it moderately well but letrozole does not, CYP3A4 is a good candidate for the protein that [11C]-vorozole is binding to in the liver.
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Chang, Thomas KH, and Rosita KY Yeung. "Effect of trans-resveratrol on 7-benzyloxy-4-trifluoromethylcoumarin O-dealkylation catalyzed by human recombinant CYP3A4 and CYP3A5." Canadian Journal of Physiology and Pharmacology 79, no. 3 (March 1, 2001): 220–26. http://dx.doi.org/10.1139/y00-130.

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Red wine concentrate has been reported to inhibit the catalytic activity of human recombinant cytochrome P450 (CYP) 3A4. Wine contains many polyphenolic compounds, including trans-resveratrol, which is also available commercially as a nutraceutical product. In the present study, we examined the in vitro effect of trans-resveratrol on human CYP3A catalytic activity by employing recombinant CYP3A4 and CYP3A5 as model enzymes and 7-benzyloxy-4-trifluoromethylcoumarin (BFC) as a CYP3A substrate. Trans-resveratrol inhibited BFC O-dealkylation catalyzed by CYP3A4 and CYP3A5 in a concentration-dependent manner. In each case, the inhibition was noncompetitive, as determined by Lineweaver-Burk and Dixon plots of the enzyme kinetic data. The apparent Ki values (mean ± SEM) for the inhibition by trans-resveratrol of BFC O-dealkylation catalyzed by CYP3A4 and CYP3A5 were 10.2 ± 1.1 µM and 14.7 ± 0.3 µM, respectively. Preincubation of trans-resveratrol with NADPH and CYP3A4 or CYP3A5 for 10 or 15 min prior to initiation of substrate oxidation did not enhance the inhibitory effect, suggesting that this compound was not a mechanism-based inactivator of CYP3A4 or CYP3A5 when BFC was used as the substrate. Overall, our study provides the first demonstration that trans-resveratrol inhibits, in vitro, a substrate oxidation reaction catalyzed by human recombinant CYP3A4 and CYP3A5.Key words: 7-benzyloxy-4-trifluoromethylcoumarin, cytochrome P450, CYP3A4, CYP3A5, 7-hydroxy-4-trifluoromethylcoumarin, nutraceutical, trans-resveratrol.
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Bořek-Dohalská, Lucie, and Marie Stiborová. "Cytochrome P450 3A activities and their modulation by α-naphthoflavone in vitro are dictated by the efficiencies of model experimental systems." Collection of Czechoslovak Chemical Communications 75, no. 2 (2010): 201–20. http://dx.doi.org/10.1135/cccc2009525.

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The knowledge on efficiencies of different in vitro systems containing cytochromes P450 (CYP) of a 3A subfamily is crucial to screen potential substrates of these CYPs. We evaluated and compared efficiencies of several in vitro CYP3A enzymatic systems to oxidize the model substrates, α-NF and testosterone, under the standardized experimental conditions. Five CYP3A systems were tested: (i) human hepatic microsomes rich in CYP3A4, (ii) hepatic microsomes of rabbits treated with a CYP3A6 inducer, rifampicine, (iii) microsomes of Baculovirus transfected insect cells containing recombinant human CYP3A4 and NADPH:CYP reductase with or without cytochrome b5 (SupersomesTM), (iv) membranes isolated from Escherichia coli, containing recombinant human CYP3A4, NADPH:CYP reductase and cytochrome b5, and (v) human CYP3A4 or rabbit CYP3A6 reconstituted with NADPH:CYP reductase with or without cytochrome b5 in liposomes. All systems oxidize testosterone to its 6β-hydroxylated metabolite and α-NF to trans-7,8-dihydrodiol and 5,6-epoxide. The most efficient systems oxidizing both compounds were CYP3A4-SupersomesTM containing cytochrome b5, followed by human hepatic microsomes. This finding suggests these systems to be suitable for general evaluating a variety of compounds as potential substrates of CYP3A4. The lowest efficiencies to oxidize α-NF and testosterone were found for CYP3A4 expressed in membranes of E. coli, and for reconstituted CYP3A4 or CYP3A6. Utilizing the tested enzymatic systems, we also explain here the discrepancies, which showed previously the controversial effects of α-NF on CYP3A-mediated reactions. We demonstrate that inhibition or stimulation of the CYP3A-mediated testosterone hydroxylation by α-NF is dictated by efficiencies of individual enzymatic systems to oxidize the CYP3A substrates.
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Fang, Jim, and Jiuxue Song. "In vitro Characterization of the Oxidation of a Pyridinium Metabolite of Haloperidol by Human Placenta: The Effect of Smoking." Journal of Pharmacy & Pharmaceutical Sciences 15, no. 4 (October 4, 2012): 538. http://dx.doi.org/10.18433/j31w20.

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Purpose. The antipsychotic drug haloperidol can be metabolised to pyridinium metabolites haloperidol pyridinium (HP+) and reduced haloperidol pyridinium (RHP+). These pyridinium metabolites were proposed to contribute to the extrapyramidal side effects of haloperidol, because they are structural analogues of N-methyl-4-phenylpyridinium (MPP+), a well-known neurotoxin. RHP+ can be oxidized to HP+ by CYP1A1. In the current study, the oxidation of RHP+ to HP+ was investigated using human placenta microsomal preparations which contain relatively high levels of CYP1A1. Methods. Cytochrome P450 isoenzymes responsible for the metabolism of RHP+ were characterized in vitro using human placenta microsomal preparations from smokers and non-smokers. Results. A comparison of the metabolic activities between smokers and non-smokers suggests that smokers had higher activities for the oxidation of RHP+. A selective antibody against CYP1A1 was a partial inhibitor of RHP+ oxidase in placenta from smokers but had no effect in placenta from non-smokers. Furafylline and ketokonazole were shown to be stronger inhibitors of the oxidation of RHP+ to HP+ in liver than in placenta. This seems to indicate important contributions of CYP1A1 and CYP3A7 as compared to CYP1A2 and CYP3A4, respectively, because furafylline and ketokonazole are stronger inhibitors of CYP1A2 and CYP3A4 than CYP1A1 and CYP3A7, respectively. Interestingly, α-naphathoflavone enhanced the metabolic activity in liver microsomes due to its activator effect on CYP3A4. On the other hand, α-naphathoflavone partially inhibited the activity in placenta microsomes, indicating a role played by CYP1A1 or CYP1A2 in the oxidation of RHP+ in placenta. Conclusions. These data indicate that CYP1A1 plays an important role in the oxidation of RHP+ to HP+ in placenta from smokers. CYP3A7 and CYP3A4 could also play important roles in the metabolism of RHP+ in placenta microsomes. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
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Dissertations / Theses on the topic "CYP3A4"

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Sethabouppha, Benjabhorn. "Inter-Individual Variation in CYP3A4 and CYP3A5- Mediated Drug Metabolism." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492887.

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Cytochrome P450 enzymes, especially those of the CYP3A family, play a major role in the metabolism of many drugs.' Patient response to drugs metabolized by CYP3A4 and CYP3A5 varies considerably and part of this variability is due to genetic polymorphism ot the CYP3A5 enzyme. In this study, human liver microsomes (HLM) were prepared from a panel of 26 liver samples and total soluble protein was evaluated. The CYP3A5 and CYP3A4 protein contents were determined by Western blotting and metabolic studies of individual HLM were performed with three selected substrates, ALP, MDZ and TST using HPLC. Results from the 26 HLM preparations revealed a high variability in CYP3A4 (366.7-1.06 pmol/mg protein, 346 fold) and CYP3A5 (4.26 -0.14 pmol/mig protein, 30 fold) content. As might be expected, the two samples with the CYP3A5*l/*3 genotype expressed higher CYP3A5 protein level than the other 24 samples (CYP3A5*3/*3) indicating the consequence of the CYP3A5*1 allele on CYP3A5 protein expression.
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Willrich, Maria Alice Vieira. "Efeitos de hipolipemiantes sobre a expressão de CYP3A4 e CYP3A5 in vitro e in vivo." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-12092012-150610/.

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Introdução: As CYP3A4 e CYP3A5 são enzimas do citocromo P450 responsáveis pela biotransformação de esteróides endógenos e vários fármacos, entre eles as estatinas. Polimorfismos nos genes CYP3A4 e CYP3A5 (CYP3A4*1B, CYP3A5*3C e CYP3A5*1D) foram associados com diferenças na resposta hipolipemiante de indivíduos tratados com atorvastatina e sinvastatina. Neste estudo foram avaliados os efeitos de hipolipemiantes sobre a expressão e a atividade de CYP3A4 e CYP3A5, em linhagens celulares HepG2 e Caco-2 e em CMSP de indivíduos hipercolesterolêmicos, e sua relação com variantes de CYP3A4 e CYP3A5. Métodos: Foram analisados 99 indivíduos normolipidêmicos (NL) e 139 hipercolesterolêmicos (HC). Os HC foram tratados com atorvastatina (10 mg/dia/4 semanas). A genotipagem das variantes CYP3A4*1B, CYP3A5*3C e CYP3A5*1D foi feita por PCR-RFLP ou sequenciamento. A análise da expressão de RNAm de CYP3A4 e CYP3A5 foi avaliada por PCR em tempo real quantitativo (PCRq). As proteínas totais de HepG2 foram avaliadas por Western Blotting. A atividade de CYP3A4 e CYP3A5 in vivo foi avaliada pela relação entre cortisol e seu metabólito, 6β-hidróxicortisol, na urina (razão 6βOH-cortisol/cortisol), por CLAE. Resultados: O perfil de expressão basal de RNAm de CYP3A4 e CYP3A5 é diferente entre HepG2 e Caco-2. Caco-2 expressa 31 vezes mais CYP3A4 e 122 vezes mais CYP3A5 que HepG2. Em células HepG2 tratadas por 12 h, a atorvastatina 20 µM aumentou a expressão de CYP3A4 em 10 vezes, em relação ao controle (p=0,006). Após 24 h de tratamento, atorvastatina (1-20 µM) aumentou a expressão de CYP3A4 em 5 a 8 vezes, nas HepG2 (p< 0,001). Para CYP3A5, a exposição por 12 h à atorvastatina 20 µM aumentou a expressão em 4 vezes em relação ao controle ( p<0,001). A exposição à sinvastatina 1,0 µM por 24 h aumentou a expressão de CYP3A4, em 2 vezes (p<0,01), em HepG2. Também se observou que, nesse tempo de tratamento, a sinvastatina (0,1 µM a 10 µM) aumentou a expressão de CYP3A5 em 2 a 4 vezes (p<0,05). A linhagem HepG2 apresenta alelos funcionais (CYP3A4*1A e CYP3A5*1A) em homozigose. A linhagem Caco-2 apresenta os alelos não funcionais CYP3A5*3C e CYP3A5*1D, em heterozigose. Também foi avaliada a expressão das proteínas CYP3A4 e CYP3A5 por Western Blotting, em células HepG2, após atorvastatina (0,1 a 20 µM) e sinvastatina (0,01 a 10 µM) por 12 e 24 h. O perfil de expressão das proteínas não diferiu com os tratamentos. Nas células mononucleares do sangue periférico (CMSP), a expressão de RNAm basal de CYP3A4 é cerca de 2,5 a 9,6 vezes maior que a expressão de CYP3A5 (p< 0,05). Observou-se correlação da expressão de CYP3A4 e CYP3A5 nessas células, antes (r2 = 0,22; p< 0,0001) e após o tratamento (r2 = 0,58; p<0,0001) com atorvastatina. A expressão basal de RNAm de CYP3A4 e CYP3A5 é maior nos indivíduos (NL) que nos indivíduos (HC) (p<0,05). A atorvastatina não influenciou a expressão de CYP3A4 e CYP3A5 em CMSP (p> 0,05). Os indivíduos NL apresentam atividade de CYP3A4 e CYP3A5 basal maior que os indivíduos HC- (p<0,0001). O tratamento com atorvastatina não alterou a atividade de CYP3A4 e CYP3A5 nos HC (p>0,05). As variantes gênicas estudadas (CYP3A4*1B, CYP3A5*3C e CYP3A5*1D) como grupos haplotípicos não afetaram a resposta ao tratamento, a expressão de RNAm ou a atividade de CYP3A4 e CYP3A5, embora o haplótipo AGT tenha expressão basal de RNAm de CYP3A5 menor que os portadores de haplótipos GAT e GAC (p<0,005). Conclusão: Os resultados deste trabalho nos permitem concluir que a atorvastatina e a sinvastatina, mas não a ezetimiba, influenciam a expressão de CYP3A4 e CYP3A5 in vitro, em linhagem derivada de hepatócitos (HepG2), e que este efeito não foi reproduzido em linhagem derivada de enterócitos (Caco-2). A expressão de CYP3A4 e CYP3A5 tem grande variabilidade interindividual, independente do grupo haplotípico de cada indivíduo, e que não é influenciada pela atorvastatina.
Background: CYP3A4 and CYP3A5 are enzymes from the cytochrome P450 resposible for the biotransformation of endogenous steroids and several drugs, e.g. statins. Polymorphisms in CYP3A4 and CYP3A5 (CYP3A4*1B, CYP3A5*3C and CYP3A5*1D) have been associated with variation of lipid-lowering response in individuals treated with atorvastatin and simvastatin. In this study we evaluated the effect of hypolipemiants on expression and activity of CYP3A4 and CYP3A5, in HepG2 and Caco-2 cell lines as well as peripheral blood mononuclear cells (PBMC) in hypercholesterolemic individuals, and their relationship with CYP3A4 and CYP3A5 variants. Methods: We analyzed 99 normolipidemic individuals (NL) and 139 hypercholesterolemic (HC). HC subjects were treated with atorvastatin (HC, 10 mg/day/4 weeks). Analysis of CYP3A4*1B, CYP3A5*3C e CYP3A5*1D variants was performed with PCR-RFLP or sequencing assays and mRNA expression of CYP3A4 and CYP3A5 with Quantitative Real-time PCR (qRT-PCR) was performed . Total protein content was extracted from HepG2 for Western Blotting experiments. Activity of CYP3A4 and CYP3A5 in vivo was evaluated by 6βOH-cortisol and cortisol ratio in urine samples, by HPLC-UV method. Results: Baseline mRNA expression is different for HepG2 and Caco-2. Caco-2 expresses 31 times more CYP3A4 and 122 times more CYP3A5 than HepG2. In HepG2 cells treated for 12h, atorvastatin 20 µM increased CYP3A4 expression in 10 times, when compared to the control (p=0.006). After 24h treatment, atorvastatin (1-20 µM) increased CYP3A4 mRNA expression in 5 to 8 times, in HepG2 (p< 0.001). To CYP3A5, exposure for 12h to atorvastatin 20 µM increased expression in 4 times when compared to the control (p<0.001). Exposure to simvastatin 1.0 µM for 24 h increased CYP3A4 expression in 2 times, (p<0.01), in HepG2. With the 24h treatment,simvastatin (0.1 µM - 10 µM) CYP3A5 showed increased mRNA expression in 2 to 4 times (p<0.05). HepG2 cell line carries homozygous functional alleles (CYP3A4*1A e CYP3A5*1A). Caco-2 carries heterozygous CYP3A5*3C and CYP3A5*1D. We evaluated the protein expression of CYP3A4 and CYP3A5 with Western Blotting in HepG2 cells, after atorvastatin (0.1 - 20 µM) and simvastatin (0.01 - 10 µM) for 12 and 24 h. The proteins profile did not change with statins treatment. In PBMC, baseline mRNA expression of CYP3A4 is approximately 2.6 to 9.5 times higher than CYP3A5 (p< 0.05). There was a correlation in expression between CYP3A4 and CYP3A5, before (r2 = 0.22; p< 0.0001) and after treatment (r2 = 0.58; p<0.0001) with atorvastatin. Baseline mRNA expression of CYP3A4 and CYP3A5 is higher in (NL) than in (HC) (p<0.05). Atorvastatin treatment did not increase CYP3A4 and CYP3A5 mRNA in PBMC (p>0.05). CYP3A4/5 activity was higher in NL subjects than in HC (p<0.0001). Atorvastatin treatment did not affect CYP3A4/5 activity in HC (p>0.05). The studied variants CYP3A4*1B, CYP3A5*3C e CYP3A5*1D analyzed as a haplotype block did not affect response to treatment, mRNA expression or activity of CYP3A4 and CYP3A5. However, AGT haplotype showed lower CYP3A5 mRNA expression levels when compared to GAC and GAT haplotypes at baseline (p<0.05). Conclusion: The results of this study allow us to conclude that atorvastatin and simvastatin, but not ezetimibe, influence the expression of CYP3A4 and CYP3A5 mRNA in vitro in HepG2 cell line, but this effect was not reproduced in Caco-2 cell line or PBMC. CYP3A4 and CYP3A5 present great interindividual variability, despite the individual´s haplotype and is not influenced by atorvastatin.
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Ciaccia, Antonio. "Investigation of the interindividual variability in hepatic cytochrome P450 CYP3A4, association with CYP3A4*1B." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0004/MQ46139.pdf.

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Tomlinson, Emma Suzanne. "Dexamethasone as a probe for CYP3A4." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337128.

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El-Sankary, Wafaa Mahmoud. "Regulation of the human CYP3A4 gene." Thesis, University of Surrey, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326904.

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Al-Shakargi, Bilall. "Variationer i allelfrekvens hos cytokrom-generna;CYP3A4*1B, CYP3A5*3 och CYP2B6*6 mellan Uganda och Tanzania." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-388608.

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1. Abstrakt:Bakgrund: Malaria är en av världens viktigaste infektionssjukdomar och det beräknas vara ca300 miljoner drabbade varje år, därför är metabolismen av läkemedel som används för attbehandla malaria såsom kinin och artemisinin värt att lägga fokus på. Cytokrom P450enzymerna har en viktig roll i metabolism av malarialäkemedel och dessa uppvisar variationinterindividuellt samt mellan olika populationer på grund av polymorfism.Syfte: Denna studie har fokuserat på att undersöka tre polymorfa gener (CYP3A4*1B,CYP3A5*3 och CYP2B6*6) hos både friska och malariasmittade barn i Uganda för attjämföra resultaten med en population i Mwanza, Tanzania. Dessa polymorfa alleler påverkarmetabolismen av artemisinin och kinin, vilket i sin tur kan förorsaka minskad/ökad ellermisslyckad klinisk effekt.Metod: Genotypning av individernas blodprov gällande dessa genvarianter undersöktesgenom laboratoriestudier med PCR som huvudsaklig metod. DNA sekvensering utfördes vidUppsala Genome Center.Resultat: Resultaten visade att allelfrekvensen i Mwanza för CYP3A4*1B var 78%respektive 16% för CYP3A5*3, medan de var 72 % respektive 50% hos populationen iUganda. Allelfrekvensen för CYP2B6*6 i Uganda var 72 % och 36 % i Mwanza, Tanzania.Sammanfattning: De flesta malariamediciner uppvisar skillnader i kinetik och dynamikvilket kräver terapeutisk läkemedelsmonitorering. Sammanfattningsvis finns det skillnaderoch variationer bland de studerade polymorfa CYP enzymer interindividuellt och mellanolikaetniska grupper.Resultatet av denna studie visade både små skillnader mellan de två studerade populationernamen även skillnader mellan individer i den studerade gruppen i Uganda.
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Bombail, Vincent. "Transcriptional control of the human CYP3A4 gene." Thesis, University of Surrey, 2003. http://epubs.surrey.ac.uk/843500/.

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CYP3A4 is the most abundant P450 enzyme expressed in the human liver and it is responsible for the metabolism of approximately 50% of all clinically administrated drugs. The CYP3A4 gene is transcriptionally regulated by xenobiotics and previous work has demonstrated the first 300bp of proximal promoter to be the minimal requirement for such activation. Several nuclear receptors (CAR, SXR) have been shown to be involved in the induction of the CYP3A4 gene. The aim of this work was to further delineate the molecular basis of CYP3A4 gene expression. In vitro DNase I footprinting was carried out using HepG2 nuclear extracts to map the sites of DNA-protein interaction within the -301/+7 region of the CYP3A4 gene. Putative protein assignment for these sites using in silico analysis revealed the potential binding of transcription factors previously shown to be involved in the regulation of other CYP genes (Sp1, HNF3 and C/EBP?) at the identified protein-DNA interaction sites. These regulatory regions were then disrupted by mutagenesis and their functional effect assessed by transient transfections of reporter gene plasmids into HuH7 hepatoma cells. Statistically significant reductions of reporter gene expression were observed when putative C/EBPa and HNF sites were altered, in both the basal and rifampicin (SXR ligand) induced states. This finding suggests the involvement of proteins binding at these sites in the regulation of the CYP3A4 gene expression. An examination of the CYP3A4 promoter (-1056/+7) from 11 human DNA samples exhibiting a 14.3 fold variability in CYP3A mediated metabolism failed to show the presence of mutations. Protein-DNA interaction analysis were carried out within the newly identified CYP3A4*IE and CYP3A4*1F alleles as well as the CYP3A4 *1B allele. The results implicate the Spl transcription factor in the regulation of the CYP3A4 gene, albeit at a more distal binding site. The findings described in this thesis suggest a substantial involvement of transcription factors other than SXR/CAR in expression of CYP3A4. Because of the polymorphic expression of several liver- and hormone-dependent transcription factors their role in CYP3A4 regulation must be taken into account to understand drug-induction mechanisms and assess variability in inter-individual drug response.
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Kluth, Dirk. "Vom Antioxidanz zum Genregulator : transkriptionelle Regulation von Phase I- und Phase II-Enzymen durch Vitamin E und antioxidative sekundäre Pflanzeninhaltsstoffe." Phd thesis, Universität Potsdam, 2006. http://opus.kobv.de/ubp/volltexte/2006/1006/.

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Nahrungsinhaltsstoffe sind im Organismus an Steuerungsprozessen und Stoffwechselvorgängen beteiligt, wobei die Mechanismen ihrer Wirkung noch nicht völlig aufgeklärt sind. Wie Vitamin E zeigen auch sekundäre Pflanzeninhaltsstoffe in Zellsystemen sowie in vivo eine Reihe biologischer Wirkungen, deren Erklärung jedoch häufig auf ihre antioxidative Eigenschaft reduziert wird. Ziel der Dissertation war es, den Einfluss von Vitamin E und anderen Pflanzeninhaltsstoffen (in Form von Pflanzenextrakten oder isolierten sekundären Pflanzeninhaltsstoffen, z.B. Polyphenole), die bisher alle hauptsächlich als Antioxidanz klassifiziert wurden, auf die transkriptionelle Regulation von Phase I- und Phase II-Enzymen zu untersuchen. Dazu wurde die Aktivierung des PXR (pregnane X receptor) und des Nrf2 (NF-E2-related factor-2) als zentrale Transkriptionsfaktoren der Phase I- bzw. Phase II-Enzyme getestet.

Der Einfluss von verschiedenen Vitamin E-Formen und antioxidativen Pflanzeninhaltsstoffen in Form von Reinsubstanzen (Curcumin, EGCG, Medox, Quercetin, Resveratrol und Sulforaphan) oder Pflanzenextrakten (aus Blaubeeren, Gewürznelken, Himbeeren, Nelkenpfeffer, Thymian oder Walnüssen) auf die Aktivierung von PXR und Nrf2 sowie des Promotors eines jeweiligen Zielgens (CYP3A4 bzw. GI-GPx) wurde in vitro mit Reportergenplasmiden untersucht. Es zeigte sich, dass sowohl Vitamin E-Formen als auch verschiedene sekundäre Pflanzeninhaltsstoffe PXR und/oder Nrf2 sowie die Promotoren der jeweiligen Zielgene CYP3A4 bzw. GI-GPx aktivieren. In einem Tierexperiment konnte diese genregulatorische Wirkung von Vitamin E auf die in vivo-Situation übertragen werden. In Lebern von Mäusen, deren Futter unterschiedliche Mengen von Vitamin E enthielt (Mangel-, Normal- und Überflussdiät), wurde eine direkte Korrelation zwischen der alpha-Tocopherol-Konzentration und der Cyp3a11 mRNA-Expression nachgewiesen (Cyp3a11 ist das murine Homolog zum humanen CYP3A4). Entgegen der in vitro-Situation hatte gamma-Tocotrienol in vivo einen nur kaum nachweisbaren Effekt auf die Expression der Cyp3a11 mRNA, induzierte aber die Expression der alpha-TTP mRNA. Es konnte gezeigt werden, dass Vitamin E und sekundäre Pflanzeninhaltsstoffe Phase I- und Phase II-Enzyme transkriptionell regulieren können.

Die Wirkungen des Vitamin E können sich allerdings nur entfalten, wenn die Vitamin E-Formen ausreichend vom Körper aufgenommen werden. Gegenstand der Dissertation waren daher auch Untersuchungen zur Bioverfügbarkeit (zelluläre Akkumulation und Metabolismus) verschiedener Vitamin E-Formen. Es konnte gezeigt werden, dass Unterschiede in der chemischen Struktur der Vitamin E-Formen deren zelluläre Akkumulation und Metabolisierung beeinflussen.

Unter Berücksichtigung der Ergebnisse der Dissertation lassen sich protektive Wirkungen von antioxidativen Nahrungsinhaltsstoffen auch unabhängig von ihren antioxidativen Eigenschaften über die Induktion zelleigener Schutzsysteme, einschließlich der Phase I- und Phase II-Enzyme, erklären. Die Induktion der zelleigenen Abwehr lässt sich auch als adaptive Antwort (sog. "adaptive response") des Organismus gegenüber zellschädigenden Ereignissen betrachten.
In the organism food compounds are involved in regulatory and metabolic processes although the mechanisms of their effects have not been completely elucidated yet. Like vitamin E, secondary plant compounds have diverse biological effects, both in cell systems as well as in vivo. However, the explanation thereof is often reduced to their antioxidative capacity. The aim of this thesis was to investigate the influence of vitamin E and other plant compounds (in form of plant extracts or isolated secondary plant compounds, e.g. polyphenols), which were up to now classified primarily as antioxidants, on the transcription of phase I- and phase II-enzymes. For this, the activation of central transcription factors of the phase I- or phase II enzymes, PXR (pregnane X receptor) and Nrf2 (NF-E2-related factor-2), was tested.

The influence of different vitamin E forms and antioxidative plant compounds in form of pure substances (curcumin, EGCG, Medox, quercetin, resveratrol, and sulforaphane) or plant extracts (from blueberries, clove, raspberries, allspice, thyme, or walnuts) on the activation of PXR and Nrf2 as well as on the promoter of a respective target gene (CYP3A4 or GI-GPx) was investigated in vitro by reporter gene assays. It appeared that vitamin E forms as well as different secondary plant compounds activate PXR and/or Nrf2 as well as the promoter of the respective target genes CYP3A4 and GI-GPx. The effects of vitamin E were confirmed in vivo by an animal experiment. In livers of mice whose diet contained different amounts of vitamin E (deficient, adequate and supra-nutritional), a direct correlation between alpha-tocopherol content and Cyp3a11 mRNA expression was shown (Cyp3a11 is the murine homolog to the human CYP3A4). In contrast to the in vitro observations, gamma-tocotrienol in vivo only had a small effect on the expression of Cyp3a11 mRNA. However, it induced the expression of alpha-TTP on mRNA level. It could be shown that vitamin E and secondary plant compounds can influence the transcriptional regulation of phase I- and/or phase II-enzymes.

However, these effects of vitamin E can only be seen if the vitamin E forms are taken up by the body sufficiently. Therefore, another aim of the thesis was to investigate the bioavailability of different vitamin E forms (i.e., cellular accumulation and metabolism). It could be shown that differences in the chemical structure of vitamin E forms influence their cellular accumulation and metabolism.

Regarding the results of this thesis, protective effects of antioxidative food compounds can be explained independent of their antioxidative properties by the induction of cellular protective systems, including phase I- and phase II-enzymes. The induction of cellular defence mechanism can also be considered as an adaptive response of the organism towards cell-damaging events.
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Gratien-Debette, Marilyne. "Etude rétrospective de l'influence des polymorphismes génétiques de CYP3A4, CYP3A5 et ABCB1 des donneurs et des receveurs sur les effets des immunosuppresseurs en transplantation hépatique." Thesis, Limoges, 2015. http://www.theses.fr/2015LIMO0032/document.

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La transplantation hépatique est une technique chirurgicale maîtrisée, mais le devenir à long terme du greffon et de l’hôte doit encore être amélioré. L’étude pharmacogénétique des inhibiteurs de la calcineurine (CNI) devrait permettre de comprendre la variabilité de leurs effets thérapeutiques et toxiques. Dans un premier temps, nous avons réalisé une revue de la littérature concernant la pharmacogénétique des CNI en greffe d’organe et surtout hépatique en particulier les trois polymorphismes les plus impliqués dans la pharmacocinétique des CNI (CYP3A4*22, CYP3A5*3 et ABCB1 exons 12, 21, 26) et leurs éventuelles associations avec le devenir clinique du patient. L’état actuel des connaissances valide l’intérêt du génotype CYP3A5*3 pour adapter au mieux la posologie précoce de tacrolimus seulement en greffe rénale. Dans un second temps, nous avons mené une étude de cohorte rétrospective visant à étudier la pertinence et l’intérêt des génotypes du donneur et du receveur d’organe mentionnés précédemment, intervenant dans le métabolisme (CYP3A4*22, CYP3A5*3) et le transport membranaire (ABCB1 exons 12, 21 et 26) de la cyclosporine et du tacrolimus en transplantation hépatique. 170 patients avec un suivi de plus de 10 ans en moyenne ont été inclus. Les principaux résultats montrent que : l’allèle CYP3A5 *1 du receveur était associé significativement à un risque plus élevé de perte de greffon à long terme comparé à l’allèle CYP3A5 *3 ; l’allèle TT de l’exon 12 d’ABCB1 du receveur était associé à un risque moins élevé de rejet chronique ; et l’exposition à des doses élevées de CNI, la valeur initiale de la fonction rénale et l’âge du receveur étaient également indépendamment associés au risque d’altération de la fonction rénale. La caractérisation de ces marqueurs pharmacogénétiques en transplantation hépatique pourrait permettre d’adapter les traitements immunosuppresseurs pour chaque patient transplanté. D’autres voies de recherche (pharmacogénétique de la voie calcineurine, biomarqueurs précoces des lésions du greffon, ...) seront nécessaires pour identifier un profil personnalisé pour chaque greffé afin d’adapter au mieux la stratégie thérapeutique à long terme
Liver transplantation is now a well mastered surgery with standardized procedures, but the long-term clinical outcomes of the graft and the patient remain uncertain. The pharmacogenetic study of the calcineurin inhibitors (CNI) cyclosporine and tacrolimus should help to understand the variability of their pharmacokinetics and therapeutic or side effects. In the first part of this work, we reviewed the main pharmacogenetic studies of CNI in liver transplantation, focusing on the three polymorphisms mostly involved in CNI pharmacokinetics (CYP3A4*22, CYP3A5*3 et ABCB1 exons 12, 21, 26) and their possible associations with clinical outcomes. To date, the only pharmacogenetic test consensually recommended in organ transplantation is the CYP3A5*3 variant for a better selection of the initial tacrolimus dose in kidney transplantation. The second part of this work was a retrospective cohort study in liver transplantation to investigate the influence of the above mentioned donor’s and recipient’s genotypes, involved in the metabolism (CYP3A4*22, CYP3A5*3) and the membrane transport (ABCB1 exons 12, 21 and 26) of cyclosporine and tacrolimus. 170 patients were enrolled in this study with a mean follow-up of more than ten years. Our main results are that: the recipient CYP3A5*1 allele was associated with a higher risk of graft loss than the CYP3A5*3 allele; the recipient ABCB1 exon 12 TT genotype was associated with a lower risk of chronic rejection than the CC genotype; overexposure to CNI, initial renal function and recipient age were associated with a higher risk of post-transplantation renal dysfunction. No genetic factor was associated with patient survival, acute rejection, liver function tests, recurrence of viral or other initial liver disease, or nephrotoxicity. Prospective characterization of both recipient and donor CYP3A4, CYP3A5 and ABCB1 polymorphisms could help to optimize immunosuppressive therapy for each candidate to liver transplantation. Further studies (pharmacogenetics of calcineurin pathway, early biomarkers of graft dysfunction, ...), should help to define a personalized profile for each transplant patient in order to best adapt the immunosuppressive strategy on the long term
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Nem, Dieudonné [Verfasser]. "In vivo and in vitro investigation of the tissue-specific activity of the human CYP3A4 and CYP3A5 promoters / Dieudonné Nem." Mainz : Universitätsbibliothek Mainz, 2012. http://d-nb.info/1019667125/34.

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Books on the topic "CYP3A4"

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Pastrakuljic, Aleksandra. In vitro activities associated with CYP1A1 and CYP1A2 in normal human liver specimens. Ottawa: National Library of Canada, 1996.

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Merle, Olivier. A 13CO2 breath test for cytochrome P450 CYP3A based on tamoxifen N-demethylation. Leicester: De Montfort University, 1999.

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Zhou, Yang Thomas. Assessment of caffeine as a probe for CYP1A2 activity. Ottawa: National Library of Canada, 1995.

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Goodz, Shari D. Investigating aspects of CYP2A6 in Caucasian and African American smokers. Ottawa: National Library of Canada, 2002.

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Zeman, Marilyn Vera. evaluation of coumarin as an in vivo measure of CYP2A6 activity. Ottawa: National Library of Canada, 1998.

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Andreou, Efrosini Roseann. Analysis of CYP7A1 gene regulation in HepG2 cells by reverse-transcriptase polymerase chain reaction. Ottawa: National Library of Canada = Bibliothèque nationale du Canada, 1999.

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Dortok, E. Desiree. Analysis of the possible therapeutic use of CYP2A6 inhibition with methoxsalen in smoking cessation. Ottawa: National Library of Canada, 2001.

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Nowak, Maciej P. Comparison of polymorphic CYP2D6, CYP2C19 and CYP2A6 in Canadian Native Indian, Caucasian and Chinese populations. Ottawa: National Library of Canada = Bibliothèque nationale du Canada, 1999.

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Chart, Thomas E. Flow effects on humpback chub (Gila cypha) in Westwater Canyon / Thomas E. Chart and Leo Lentsch. Moab, Utah: Utah Divison of Wildlife Resources, Moab Native Fishes Field Office, 1999.

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Investigation of the interindividual variability in hepatic cytochrome P450 CYP3A4: Association with CYP3A4*1B. Ottawa: National Library of Canada, 1999.

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Book chapters on the topic "CYP3A4"

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DeCou, Jennifer, Nathaniel Birgenheier, and Randal O. Dull. "CYP3A4: The Workhorse." In A Case Approach to Perioperative Drug-Drug Interactions, 37–40. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4614-7495-1_7.

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Chen, Yuan, and Adrian J. Fretland. "Evaluation of Time-Dependent CYP3A4 Inhibition Using Human Hepatocytes." In Methods in Pharmacology and Toxicology, 269–79. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-742-6_16.

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Sinz, Michael W. "Avoiding PXR and CAR Activation and CYP3A4 Enzyme Induction." In Topics in Medicinal Chemistry, 159–90. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/7355_2013_24.

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Zhang, J. George, and David M. Stresser. "Assessment of CYP3A4 Time-Dependent Inhibition in Plated and Suspended Human Hepatocytes." In Methods in Pharmacology and Toxicology, 255–68. Totowa, NJ: Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-742-6_15.

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Takahashi, Kyoko, Hideyasu Matsuda, Kayoko Kinoshita, Norikazu Matsunaga, Akihiko Sumita, Takahisa Matsuda, Koichi Takahashi, and Junichi Azuma. "Modulation of Taurine on CYP3A4 Induction by Rifampicin in a HepG2 Cell Line." In Advances in Experimental Medicine and Biology, 237–44. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0077-3_30.

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Erratico, Claudio A., Anand K. Deo, and Stelvio M. Bandiera. "Regioselective Versatility of Monooxygenase Reactions Catalyzed by CYP2B6 and CYP3A4: Examples with Single Substrates." In Advances in Experimental Medicine and Biology, 131–49. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-16009-2_5.

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Luu, Alice, Brian C. Foster, Kristina L. McIntyre, Teresa W. Tam, and John T. Arnason. "Pharmacogenetics in Potential Herb–Drug Interactions: Effects of Ginseng on CYP3A4 and CYP2C9 Allelic Variants." In The Biological Activity of Phytochemicals, 59–65. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-7299-6_5.

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Roussel, Danielle, Emily Hagn, and Randal O. Dull. "CYP1A2: The Switch-hitter." In A Case Approach to Perioperative Drug-Drug Interactions, 41–44. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4614-7495-1_8.

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Moorthy, Bhagavatula. "Chapter 3. The CYP1A Subfamily." In Issues in Toxicology, 97–135. Cambridge: Royal Society of Chemistry, 2008. http://dx.doi.org/10.1039/9781847558428-00097.

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Raunio, Hannu, Jukka Hakkola, and Olavi Pelkonen. "Chapter 5. The CYP2A Subfamily." In Issues in Toxicology, 150–77. Cambridge: Royal Society of Chemistry, 2008. http://dx.doi.org/10.1039/9781847558428-00150.

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Conference papers on the topic "CYP3A4"

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Georgiev, Kaloyan, Maya Radeva, and Tamara Pajpanova. "Potent inhibition of CYP3A4 by the endomorphin-2analogues." In 35th European Peptide Symposium. Prompt Scientific Publishing, 2018. http://dx.doi.org/10.17952/35eps.2018.283.

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Potter, David A., Zhijun Guo, Ranjana Mitra, Monica Milani, Mariangellys Rodriguez, Li Ding, Robin Bliss, et al. "Abstract 357: CYP3A4 Activates Stat3 in ER + breast cancer." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-357.

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Georgiev, Kaloyan, Maya Radeva, Anelia Balacheva, Sylvia Michaylova, and Tamara Pajpanova. "Modulation of CYP3A4 by the RGD- and Neurotensin(8-13)-analogues." In 35th European Peptide Symposium. Prompt Scientific Publishing, 2018. http://dx.doi.org/10.17952/35eps.2018.215.

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Mooiman, Kim D., Roel F. M. Maas-Bakker, Jos H. Beijnen, Jan H. M. Schellens, and Irma Meijerman. "Abstract 3791: Milk thistle as an inhibitor of PXR-mediated CYP3A4 induction." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3791.

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Gorjala, Priyatham, Oscar Goodman Jr, and Ranjana Mitra. "Abstract 1805: CYP3A4 regulation of androgen receptor signaling in ER+ breast cancer." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1805.

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Guo, Zhijun, Beverly Norris, Jonathan Henriksen, Monique Morgan, Michael Maher, Robert Schumacher, Robin Bliss, et al. "Abstract 82: CYP3A4 promotes mammary carcinoma angiogenesis in a cell iIntrinsic fashion." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-82.

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Andrade, Carolina, Flávia Silva, Ekaterina Varlamova, and Rodolpho Braga. "Development of QSAR models for identification of CYP3A4 substrates and inhibitors." In MOL2NET, International Conference on Multidisciplinary Sciences. Basel, Switzerland: MDPI, 2015. http://dx.doi.org/10.3390/mol2net-1-b034.

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Ahmed, Atif, Hamid Zia, Graeme I. Murray, Carrie A. Vyhlidal, J. Steven Leeder, and Marilyn M. Bui. "Abstract 415: Cytochrome CYP3A4 expression may predict metastasis in Ewing's sarcoma family of tumors." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-415.

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Guo, Zhijun, Ranjana Mitra, Monica Milani, Mariangellys Rodriguez, Douglas Yee, Deepali Sachdev, and David A. Potter. "Abstract 2288: CYP3A4 monoxygenase regulates IGF-1 signaling in ER-positive breast cancer cells." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2288.

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Chen, Yakun, Yong Tang, Gregory Thomas Robbins, and Daotai Nie. "Abstract 2667: Inhibition of CYP3A4 expression by camptothecin via blocking activation of pregnane X receptor." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-2667.

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Reports on the topic "CYP3A4"

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Casabar, Richard C., Andrew D. Wallace, Ernest Hodgson, and Randy L. Rose. Metabolism of Endosulfan-Alpha by Human Liver Microsomes and its Utility as a Simultaneous In Vitro Probe for CYP2B6 and CYP3A4. Fort Belvoir, VA: Defense Technical Information Center, March 2006. http://dx.doi.org/10.21236/ada445178.

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Dudley, A., M. M. Peden-Adams, J. E. Daly, and D. E. Keil. JP-8 Jet Fuel Induces CYP2B1, CYP2BE1, and GSTPI but not CYP1A1 in Murine Liver. Fort Belvoir, VA: Defense Technical Information Center, March 2001. http://dx.doi.org/10.21236/ada402064.

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Lamb, Dolores J. Enhancement of Vitamin D Action in Prostate Cancer through Silencing of CYP24. Fort Belvoir, VA: Defense Technical Information Center, February 2009. http://dx.doi.org/10.21236/ada502323.

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Lamb, Dolores. Enhancement of Vitamin D Action in Prostate Cancer through Silencing of CYP24. Fort Belvoir, VA: Defense Technical Information Center, February 2011. http://dx.doi.org/10.21236/ada550337.

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Lamb, Dolores J. Enhancement of Vitamin D Action in Prostate Cancer through Silencing of CYP24. Fort Belvoir, VA: Defense Technical Information Center, February 2010. http://dx.doi.org/10.21236/ada625333.

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Lamb, Dolores J. Enhancement of Vitamin D Action in Prostate Cancer through Silencing of CYP24. Fort Belvoir, VA: Defense Technical Information Center, February 2008. http://dx.doi.org/10.21236/ada482357.

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Draeger, E., B. Bennion, F. Gygi, and F. Lightstone. Understanding the Mechanism of Human P450 CYP1A2 Using Coupled Quantum-Classical Simulations in a Dynamical Environment. Office of Scientific and Technical Information (OSTI), February 2006. http://dx.doi.org/10.2172/899113.

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Goulet, C. T., and K. E. LaGory. Annotated bibliography for the humpback chub (Gila cypha) with emphasis on the Grand Canyon population. Office of Scientific and Technical Information (OSTI), October 2009. http://dx.doi.org/10.2172/965762.

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Carlson, E. A., Y. Li, and J. T. Zelikoff. Inhibition of CYP1A-Mediated Metabolism of Benzo(A)Pyrene (BAP): Effects Upon BAP-Induced Immunotoxicity in Japanese Medaka (Oryzias Latipes). Fort Belvoir, VA: Defense Technical Information Center, March 2001. http://dx.doi.org/10.21236/ada402076.

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