Effect of naproxen on the kinetics of elimination and anticoagulant activity of a single dose of warfarin

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Abstract
The purpose of this investigation was to determine the effect of the nonsteroidal anti‐inflammatory drug naproxen on the elimination kinetics and anticoagulant activity of warfarin. Ten healthy men received one oral dose of 50 mg racemic warfarin alone and with naproxen, 375 mg twice daily for 17 days beginning 10 days before warfarin. Naproxen administration caused a small but statistically significant increase in the free fraction of warfarin in serum but had no significant effect on the total clearance, volume of distribution, half‐life, and anticoagulant activity of warfarin. Warfarin, on the other hand, apparently enhances the serum protein binding of naproxen. There was substantial intersubject variation but very little intrasubject variation in the anticoagulant effect of warfarin. The intersubject variation of the anticoagulant effect was not related to the elimination kinetics of warfarin.