No effect of short-term omeprazole intake on acenocoumarol pharmacokinetics and pharmacodynamics

Abstract

Aims - To investigate the effect of omeprazole on the pharmacokinetics of R- and S-acenocoumarol and on their combined anticoagulant activity. Methods - Eight healthy male subjects completed a double-blind, randomized, placebo-controlled, two-way cross-over study. Subjects were given either omeprazole 40 mg or placebo once daily for 3 days. On day 2 of each study period, a single 10 mg oral dose of racemic acenocoumarol was administered and venous blood samples were collected for pharmacokinetic and pharmacodynamic assessments. A wash-out period of 2 weeks separated the two study periods. Results - The pharmacokinetics of R- and S-acenocoumarol (AUC 3016 ± 221 and 233 ± 14 ng ml-1 h, respectively) did not change after omeprazole (AUC 2929 ± 256 and 220 ± 18 ng ml-1 h, respectively). Anticoagulant activity (INR(max) 1.7 ± 0.1) was unaffected by co-administration of omeprazole (INR(max) 1.7 ± 0.1). Conclusions - The short-term intake of omeprazole does not affect acenocoumarol pharmacokinetics or pharmacodynamics. These data differ from the results of previous studies on the effect of omeprazole on warfarin, suggesting a different in vivo interaction profile of omeprazole on acenocoumarol than on warfarin. Drug interaction studies with oral anticoagulants should not be restricted to the use of warfarin.