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.
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