J N de Hoon1, H H Thijssen, A J Beysens, L M Van Bortel. 1. Department of Pharmacology, Maastricht University, Cardiovascular Research Institute Maastricht, and Clinical Pharmacy, Academic Hospital Maastricht, The Netherlands.
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 (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.
RCT Entities:
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.
Authors: Tudor Radu Pop; Ştefan Cristian Vesa; Adrian Pavel Trifa; Sorin Crişan; Anca Dana Buzoianu Journal: Eur J Clin Pharmacol Date: 2013-06-18 Impact factor: 2.953
Authors: M L Becker; W P J Franken; F Karapinar; R Verzijl-Zeegers; T Schalekamp; R T M van der Hoeven Journal: Eur J Clin Pharmacol Date: 2015-09-24 Impact factor: 2.953