The mechanism of the warfarin-rifampin drug interaction in humans

Clin Pharmacol Ther. 1987 Oct;42(4):388-94. doi: 10.1038/clpt.1987.168.


The mechanism of the drug interaction in humans between warfarin and rifampin was investigated by monitoring the elimination kinetics and metabolic disposition of a single oral dose of pseudoracemic warfarin by GC/MS. The decrease in hypoprothrombinemia observed with concomitant administration of therapeutic doses of rifampin was accompanied by a substantial decrease in the elimination half-lives of both warfarin enantiomers. Rifampin increased the clearance of (R)-warfarin threefold and the clearance of (S)-warfarin twofold. The excretion profiles for warfarin and its metabolites in urine and feces were similar for both control and treated subjects with the exception that 4'-hydroxywarfarin (stereoselective for the (S)-enantiomer) was observed when rifampin was administered. 4'-Hydroxywarfarin is a metabolite of the drug hitherto undetected in vivo in humans. Based on formation clearance values estimated for 6-, 7-, and 8-hydroxywarfarin, rifampin appears to increase the clearance of the parent drug by induction of the cytochrome P-450 isozyme(s) responsible for aromatic hydroxylation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Carbon Radioisotopes
  • Chromatography, Gas
  • Drug Interactions
  • Half-Life
  • Humans
  • Hydroxylation
  • Male
  • Mass Spectrometry
  • Prothrombin Time
  • Rifampin / pharmacology*
  • Stereoisomerism
  • Warfarin / metabolism
  • Warfarin / pharmacokinetics
  • Warfarin / pharmacology*


  • Carbon Radioisotopes
  • Warfarin
  • Rifampin