title: Distinct effects of omeprazole and rabeprazole on the tacrolimus blood concentration in a kidney transplant recipient.
abstract: Proton-pump inhibitors (PPIs, e.g. omeprazole and rabeprazole) are often administered to transplant patients as a treatment or prophylaxis for ulcers after surgery. Since tacrolimus and PPIs share the CYP3A4 system for metabolism, pharmacokinetic interactions are anticipated when they are administered simultaneously. We present a Japanese male patient who underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. The concentration/dose (C/D) ratio for tacrolimus was markedly higher during the period of treatment with omeprazole than ranitidine or rabeprazole. The results of liver functional tests were within the normal range during the use of these three antacid drugs. Since the higher C/D ratio for tacrolimus when omeprazole was being administered did not result from a decrease in the elimination of tacrolimus due to hepatic dysfunction, drug interaction between omeprazole and tacrolimus was strongly suspected. The present case indicates that rabeprazole can be used safely in place of omeprazole in kidney transplant recipients receiving tacrolimus.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Takahashi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yano
authors.forename: Yuga
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: Toshiya
authors.initials: T
authors.lastname: Katsura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ito
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009853:Omeprazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D064750:Rabeprazole; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole; D016559:Tacrolimus