LOSARTAN DOES NOT AFFECT THE PHARMACOKINETICS AND PHARMACODYNAMICS OFWARFARIN

Losartan, an orally active, nonpeptide angiotensin II receptor antagon ist is being developed as a therapeutic agent for the treatment of hyp ertension and heart failure. Many patients requiring anticoagulant the rapy with warfarin also may have hypertension or heart failure, and th us, are potential candidates for losartan therapy. This study was desi gned to investigate whether losartan at likely dosage levels would alt er the anticoagulant response to warfarin. In a two-period, placebo-co ntrolled, randomized, crossover study, ten healthy male subjects recei ved a single oral dose of 30 mg warfarin sodium on the seventh day of a 13-day treatment with losartan, 100 mg daily by mouth, or placebo. M ultiple plasma samples were collected over a 6-day period after both w arfarin doses for the measurements of R- and S-warfarin concentrations and prothrombin times, The pharmacokinetics of R- and S-warfarin were comparable in the absence and presence of losartan (no significant ef fects of losartan on area under the curve, C-max, or t(max)). Losartan also had no significant effect on the anticoagulant effect of warfari n, as assessed by the area under the prothrombin time versus time curv e and the maximum response for prothrombin time. The lack of pharmacok inetic or pharmacodynamic interaction between warfarin and losartan ob served in this investigation suggests that a clinically important inte raction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.