title: Interaction between tacrolimus and lansoprazole, but not rabeprazole in living-donor liver transplant patients with defects of CYP2C19 and CYP3A5.
abstract: We report different effects of administration of proton pump inhibitors on tacrolimus blood concentration in two living-donor liver transplant patients. In case 1, a 51-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation, and tacrolimus was orally administered. Omeprazole (40 mg/day) was introduced intravenously between postoperative days 5 and 6, and oral lansoprazole (30 mg/day) was introduced from day 6, leading to an increase in the concentration/dose ratio of tacrolimus from day 10. In case 2, a 41-year-old living-donor liver transplant woman received tacrolimus, and co-administered with omeprazole (40 mg/day) intravenously during 7 days immediately after surgery. During this period, trough concentration of tacrolimus was high, but the concentration/dose ratio of tacrolimus was gradually decreasing with time. Switched to rabeprazole (10 mg/day) orally on the postoperative 8th day, the concentration/dose ratio of tacrolimus remained low, indicating little drug-drug interaction between tacrolimus and rabeprazole. In both cases, the genotypes of CYP2C19 and CYP3A5 were defective both in the graft liver and in the native intestine. A drug-drug interaction between rabeprazole and tacrolimus was not observed in this case study presented, suggesting that this combination could be safely used in tacrolimus therapy after liver transplantation.
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: Yasuhiro
authors.initials: Y
authors.lastname: Ogura
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Oike
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Takada
authors.forename: Toshiya
authors.initials: T
authors.lastname: Katsura
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology*; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000502:physiology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D064747:Lansoprazole; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000502:physiology*; D064750:Rabeprazole; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000276:Adjuvants, Immunologic; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus