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.
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