Absence of influence of concomitant administration of rabeprazole on the pharmacokinetics of tacrolimus in adult living-donor liver transplant patients: A case-control study

Keiko Hosohata, Satohiro Masuda, Atsushi Yonezawa, Mitsuhiro Sugimoto, Yasutsugu Takada, Toshimi Kaido, Yasuhiro Ogura, Fumitaka Oike, Uemoto Shinji, Ken Ichi Inui

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Abstract

This study assesses the effects of rabeprazole on the pharmacokinetics of tacrolimus, considering the cytochrome P450 (CYP) 2C19 and CYP3A5 genotypes of living-donor liver transplant patients (native intestine) and their corresponding donors (graft liver). We examined the concentration/dose ratio of tacrolimus in transplant patients treated with (n=17) or without (n=38) rabeprazole at 10 mg/day on postoperative days 22-28. A stratified analysis revealed no significant differences between the control and rabeprazole groups in the median (range) concentration/dose ratio of tacrolimus [(ng/mL)/(mg/day)] for CYP2C19 extensive/intermediate metabolizers [2.71 (1.00-6.15) versus 2.55 (0.96-9.25); P=0.85] and for poor metabolizers [4.92 (2.44-7.00) versus 3.82 (2.00-7.31); P=0.68], respectively. Even based on the classification of CYP2C19 genotypes of donors, no significant difference in the concentration/dose ratio of tacrolimus was found for the two groups (CYP2C19 extensive/intermediate metabolizers, P=0.52; poor metabolizers, P=0.51). The same was observed for CYP3A5*1 carriers (P=0.97 for native intestine; P= 0.87 for graft liver) and CYP3A5*3/*3 carriers (P=0.89 for native intestine; P=0.56 for graft liver). These findings suggest a safer dosing and monitoring of tacrolimus coadministered with rabeprazole early on after liver transplantation regardless of the CYP2C19 and CYP3A5 genotypes of transplant patients and their donors.

Original languageEnglish
Pages (from-to)458-463
Number of pages6
JournalDrug metabolism and pharmacokinetics
Volume24
Issue number5
DOIs
Publication statusPublished - Jan 1 2009

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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