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

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Robertson P Jr, Hellriegel ET, Arora S, Nelson M

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.

PubMed ID

11831544 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Modafinil	Cytochrome P450 2C9	Protein	Humans	Unknown	Inhibitor Inducer	Details