The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin

The oral anticoagulant warfarin is clinically administered as a racemic mix ture of two enantiomers, (R) and (S). Many relevant drug interactions with werfarin have been attributed to the specific metabolic inhibition of the e limination of the more pharmacologically active (S)-enantiomer. To investig ate reports that acetaminophen can potentiate the anticoagulant effect of w alfarin, 20 healthy male volunteers were each given single oral 20 mg doses of racemic warfarin on three separate occasions: (1) alone, (2) after 1 da y of acetaminophen (4 gld), and (3) after 2 weeks of acetaminophen (4 g/d). The urinary excretion pattern of acetaminophen and its metabolites tvas no t significantly altered over ifs course of administration. The (R)- and (S) -enantiomers of warfarin exhibited significantly different pharmacokinetic properties. However, acetaminophen did not alter the disposition of either (R)- or (S)-warfarin. All subjects exhibited a pharmacodynamic response to racemic warfarin. The response was not significantly altered in the presenc e of acute or chronic acetaminophen dosing, as assessed by prothrombin time and factor VII concentrations. Journal of Clinical Pharmacology, 1999;39:6 8-75 (C) 1999 the American College of Clinical Pharmacology.