Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers

J Clin Pharmacol. 2002 Feb;42(2):205-14. doi: 10.1177/00912700222011120.


Modafinil has been reported to produce a concentration-related suppression of CYP2C9 activity in vitro in primary cultures of human hepatocytes. To determine whether this effect occurs in vivo, the pharmacokinetics of (S)-warfarin was investigated after single oral doses of racemic warfarin (5 mg; COUMADIN) in a placebo-controlled, single-blind, single-period study in 28 volunteers. Subjects received an oral dose of warfarin prior to administration of modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo and they received another after 4 weeks of treatment. Treatment with modafinil did not significantly alter the pharmacokinetics of (S)- or (R)-warfarin relative to placebo. Since (S)-warfarin is predominantly metabolized via CYP2C9, the results indicate that the marked suppression of CYP2C9 activity in vitro does not translate into a similar effect clinically. However, limitations arising from investigation of single doses of warfarin preclude global conclusions about the potential for more subtle interactions after chronic warfarin administration.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants / adverse effects
  • Anticoagulants / blood
  • Anticoagulants / pharmacokinetics*
  • Area Under Curve
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / pharmacokinetics
  • Benzhydryl Compounds / pharmacology*
  • Biotransformation
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / pharmacokinetics
  • Central Nervous System Stimulants / pharmacology*
  • Chromatography, High Pressure Liquid
  • Drug Interactions
  • Female
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Modafinil
  • Patient Compliance
  • Prothrombin Time
  • Single-Blind Method
  • Stereoisomerism
  • Warfarin / adverse effects
  • Warfarin / blood
  • Warfarin / pharmacokinetics*


  • Anticoagulants
  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Warfarin
  • Modafinil