title: Losartan does not affect the pharmacokinetics and pharmacodynamics of warfarin.
abstract: Losartan, on orally active, nonpeptide angiotensin II receptor antagonist is being developed as a therapeutic agent for the treatment of hypertension and heart failure. Many patients requiring anticoagulant therapy with warfarin also may have hypertension or heart failure, and thus, are potential candidates for losartan therapy. This study was designed to investigate whether losartan at likely dosage levels would alter the anticoagulant response to warfarin. In a two-period, placebo-controlled, randomized, crossover study, ten healthy male subjects received 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. Multiple plasma samples were collected over a 6-day period after both warfarin 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 effects of losartan on area under the curve, Cmax, or tmax). Losartan also had no significant effect on the anticoagulant effect of warfarin, as assessed by the area under the prothrombin time versus time curve and the maximum response for prothrombin time. The lack of pharmacokinetic or pharmacodynamic interaction between warfarin and losartan observed in this investigation suggests that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.
authors.affiliation: Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Kong
authors.forename: L
authors.initials: L
authors.lastname: Tomasko
authors.forename: S A
authors.initials: SA
authors.lastname: Waldman
authors.forename: B
authors.initials: B
authors.lastname: Osborne
authors.forename: P J
authors.initials: PJ
authors.lastname: Deutsch
authors.forename: M R
authors.initials: MR
authors.lastname: Goldberg
authors.forename: T D
authors.initials: TD
authors.lastname: Bjornsson
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019808:Losartan; D008297:Male; D011517:Prothrombin Time; D011945:Receptors, Angiotensin / Q000378:metabolism; D013237:Stereoisomerism; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014859:Warfarin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000925:Anticoagulants; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014859:Warfarin; D019808:Losartan