Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers

Montelukast, a cysteinyl leukotriene receptor antagonist, is being develope d for the treatment of asthma and related diseases. This study was designed to evaluate whether montelukast at clinically used dosage levels would int erfere with the anticoagulant effect of warfarin. In a two-period, double-b lind, randomized crossover study 12 healthy male subjects received a single oral dose of 30 mg warfarin on the 7th day of a la-day treatment with mont elukast, 10 mg daily by mouth, or a placebo. Montelukast had no significant effect on the area under the plasma concentration-time curves and peak pla sma concentrations of either R- or S-warfarin. However, slight but statisti cally significant decreases in time to peak concentration of both warfarin enantiomers and in elimination half-life of the less potent R-warfarin were observed in the presence of montelukast. These changes were not considered as clinically relevant. Montelukast had no significant effect on the antic oagulant effect of warfarin, as assessed by the international normalized ra tio (INR) for prothrombin time (AUC(0-144) and INR maximum). The results of this study suggest that a clinically important interaction between these d rugs is unlikely to occur in patients requiring concomitant administration of both drugs. (C) 1999 the American College of Clinical Pharmacology.