Losartan Does Not Affect the Pharmacokinetics and Pharmacodynamics of Warfarin

Ah‐Ng Tony Kong, Lisa Tomasko, Scott A. Waldman, Barbara Osborne, Paul J. Deutsch, Michael R. Goldberg, Thorir D. Bjornsson

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Losartan, an 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. 1995 American College of Clinical Pharmacology

Original languageEnglish (US)
Pages (from-to)1008-1015
Number of pages8
JournalThe Journal of Clinical Pharmacology
Volume35
Issue number10
DOIs
StatePublished - Oct 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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