Omeprazole is a proton pump inhibitor with a number of pharmacokinetic drug interactions due to interference with cytochrome P450. Some studies show absence of relevant interaction between omeprazole and cyclosporine, but little is known about possible interactions between omeprazole and tacrolimus. In vitro studies suggest such interference, but no clinical data are available so far. We assessed interactions between omeprazole and tacrolimus among patients fulfilling two criteria: (1) renal allograft recipients receiving immunosuppression based on tacrolimus and acid-related disorder prophylaxis with omeprazole 20 mg/d since the day of the transplant procedure and (2) stopped omeprazole when it was considered unnecessary. Fifty-one transplant recipients received concomitant immunosuppression with MMF-prednisone (n = 47) or azathioprine-prednisone (n = 1), or rapamycin-prednisone (n = 2) or only prednisone (n = 1). omeprazole was stopped after 6.2 +/- 3 months of treatment. Tacrolimus doses and levels were recorded during 3 outpatient visits before omeprazole withdrawal (Pre3/Pre2/Pre1), at the withdrawal visit (Susp), and at 3 visits after withdrawal (Pos1/Pos2/Pos3). Weight gain was significant (72.5 +/- 13 kg Pre3; 73.4 +/- 13 kg Susp; 74 +/- 12.9 kg Pos3, P < .0001) and serum creatinine (SCr) decreased (1.70 +/- 0.49 mg/dL Pre3; 1.63 + 0.49 Susp; 1.58 +/- 0.48 Pos3, P < .0001). The progressive decrease in tacrolimus doses and levels was significant (ANOVA including the 7 visits <0.01 in all cases); whereas the level/dose ratio remained constant. Tacrolimus doses and levels continued a slow, progressive and significant decrease without any relevant change between visits during on versus off omeprazole. This clinical-analytical study supported the conclusion that an omeprazole-tacrolimus interaction is not clinically relevant. Despite possible competition or interaction at the molecular level, clinical management was not significantly affected in renal allograft recipients.