PMID: 15226679Jul 1, 2004Paper

CYP3A5*1-carrying graft liver reduces the concentration/oral dose ratio of tacrolimus in recipients of living-donor liver transplantation

Pharmacogenetics
Maki GotoKen-Ichi Inui

Abstract

Tacrolimus is widely used for immunosuppressive therapy after organ transplantation, but its pharmacokinetics shows such great interindividual variation that control of its blood concentration is difficult. We have previously reported that an intestinal P-glycoprotein (MDR1) contributes to this variation as an absorptive barrier, but the role of hepatic metabolism is not clear. In this study, we have evaluated the genotypes of MDR1 and cytochrome P450 (CYP) 3A in donor and recipient, and the influence of polymorphisms on mRNA expression and the tacrolimus concentration/dose (C/D) ratio in recipients of living-donor liver transplantation (LDLT). The expression level of MDR1 and tacrolimus C/D ratio were not affected by either MDR1 C3435T or G2677T/A. The CYP3A4*1B genotype was not detected, but the CYP3A5*3 genotype had an allelic frequency of 76.3%. The mRNA level of CYP3A5 was significantly reduced by the *3/*3 genotype, and the tacrolimus C/D ratio was decreased in recipients engrafted with partial liver carrying CYP3A5*1/*1 genotype. An analysis of the combination of intestinal MDR1 level and liver CYP3A5 genotype revealed that the tacrolimus C/D ratio was lower in the group with higher MDR1 levels regardless of CYP3A5 genot...Continue Reading

References

Sep 1, 1990·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·C Cordon-CardoM R Melamed
Dec 1, 1995·Clinical Pharmacokinetics·R VenkataramananT Starzl
Nov 23, 1996·Lancet·P A AndrewsR W Chang
Apr 13, 1999·Lancet·M D DentonM H Sayegh
Aug 15, 2001·Clinical Pharmacology and Therapeutics·R B KimG R Wilkinson
Nov 9, 2001·European Journal of Clinical Pharmacology·S FukatsuK Inui
Dec 12, 2001·Pharmacogenetics·E HustertL Wojnowski
Jun 18, 2002·Molecular Pharmacology·Chava Kimchi-SarfatyMichael M Gottesman
Jun 29, 2002·Journal of the American Society of Nephrology : JASN·Michael SiegsmundHiltrud Brauch
Aug 22, 2002·Clinical Pharmacology and Therapeutics·Yasuo KurataKenji Otsubo
Sep 14, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ina KochLeszek Wojnowski
Oct 3, 2002·Annual Review of Pharmacology and Toxicology·Matthias SchwabMartin F Fromm
Oct 31, 2002·Advanced Drug Delivery Reviews·Jatinder K LambaKenneth E Thummel
Oct 31, 2002·Advanced Drug Delivery Reviews·Martin F Fromm
Jun 5, 2003·Biochemical Pharmacology·Naomi MoritaKazuo Nakayama
Sep 27, 2003·Toxicology·Munir Pirmohamed, B Kevin Park
Oct 25, 2003·Oncogene·Suresh V AmbudkarMichael M Gottesman

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Citations

Jan 25, 2008·European Journal of Clinical Pharmacology·Katsuyoshi SugimotoTomonori Tateishi
Jun 29, 2010·European Journal of Clinical Pharmacology·Guillermo GervasiniJuan Antonio Carrillo
May 29, 2013·International Journal of Pharmaceutics·Noël KnopsDirk Kuypers
Jul 18, 2008·Transplantation Reviews·Hylke de Jonge, Dirk R J Kuypers
Apr 3, 2008·Nature Reviews. Drug Discovery·David A KatzLeonardo Sahelijo
Oct 6, 2005·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Matthias BüchlerPaul Keown
May 19, 2005·Pharmacogenetics and Genomics·Florent Busi, Thierry Cresteil
Jul 22, 2009·Clinical Neuropharmacology·Mohd Makmor-BakryMartin J Brodie
Oct 13, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Su-Jun LeeRon H N van Schaik
Jul 3, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masahide Fukudo
Jan 11, 2014·World Journal of Gastroenterology : WJG·Alessio ProvenzaniNatale D'Alessandro
Aug 12, 2009·Pharmacogenomics·Sukhwinder S LakhmanGene D Morse
Feb 5, 2008·Pharmacogenomics·Dany AnglicheauEric Thervet
Feb 9, 2010·Pharmacogenomics·Gilbert J Burckart, Shashi Amur
Nov 20, 2013·Clinical Pharmacokinetics·Dennis A HesselinkTeun van Gelder
Nov 30, 2012·Molecular Diagnosis & Therapy·Laure ElensTeun van Gelder
Mar 28, 2008·Therapeutic Drug Monitoring·Eric ThervetPhilippe Beaune
Nov 12, 2010·Therapeutic Drug Monitoring·Wei ZhaoEvelyne Jacqz-Aigrain
May 14, 2009·Expert Review of Molecular Diagnostics·Jian Wang
Jul 27, 2006·Expert Opinion on Drug Metabolism & Toxicology·Leszek Wojnowski, Landry K Kamdem

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