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

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.

DOI: 10.1046/j.1365-2125.1997.00600.x

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