title: No effect of short-term omeprazole intake on acenocoumarol pharmacokinetics and pharmacodynamics.
abstract: OBJECTIVE
  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.affiliation: Department of Pharmacology, Maastricht University, Cardiovascular Research Institute Maastricht, and Clinical Pharmacy, Academic Hospital Maastricht, The Netherlands.
authors.forename: J N
authors.initials: JN
authors.lastname: de Hoon
authors.forename: H H
authors.initials: HH
authors.lastname: Thijssen
authors.forename: A J
authors.initials: AJ
authors.lastname: Beysens
authors.forename: L M
authors.initials: LM
authors.lastname: Van Bortel
mesh_terms: D000074:Acenocoumarol / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D004311:Double-Blind Method; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000494:pharmacology*; D011517:Prothrombin Time; D013237:Stereoisomerism
chemical_list: D000925:Anticoagulants; D000074:Acenocoumarol; D009853:Omeprazole