title: Absence of influence of concomitant administration of rabeprazole on the pharmacokinetics of tacrolimus in adult living-donor liver transplant patients: a case-control study.
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.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Hosohata
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Takada
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kaido
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogura
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Oike
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage*; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016031:Liver Transplantation / Q000502:physiology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D064750:Rabeprazole; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus