Premium
Effect of Modafinil at Steady State on the Single‐Dose Pharmacokinetic Profile of Warfarin in Healthy Volunteers
Author(s) -
Robertson Philmore,
Hellriegel Edward T.,
Arora Sanjay,
Nelson Michael
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700222011120
Subject(s) - warfarin , pharmacokinetics , modafinil , cyp2c9 , placebo , pharmacology , medicine , oral administration , in vivo , drug interaction , anesthesia , atrial fibrillation , cytochrome p450 , metabolism , biology , alternative medicine , microbiology and biotechnology , pathology
Modafinil has been reported to produce a concentration‐related suppression of CYP2C9 activity in vitro in primary cultures of human hepatocytes. To determine whetherthis 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.