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No effect of short-term omeprazole intake on acenocoumarol pharmacokinetics and pharmacodynamics
J N de Hoon1, H H Thijssen, A J Beysens
1Department of Pharmacology, Maastricht University, Cardiovascular Research Institute Maastricht, and Clinical Pharmacy, Academic Hospital Maastricht, The Netherlands.
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 (INRmax 1.7 +/- 0.1) was unaffected by co-administration of omeprazole (INRmax 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.