Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.
BACKGROUND: Modafinil has been reported to produce a concentration-related induction of CYP3A4/5 activity in vitro in primary cultures of human hepatocytes. OBJECTIVE: Our objective was to determine whether the pharmacokinetics of steady-state ethinyl estradiol (INN, ethinylestradiol) and single-dose triazolam were altered after 4 weeks of modafinil treatment in volunteers. METHODS: This was a placebo-controlled, single-blind, single-period study in 41 female subjects who were receiving long-term treatment with an oral contraceptive that contained ethinyl estradiol (0.035 mg) and norgestimate (0.180-0.250 mg). Pharmacokinetic profiles for ethinyl estradiol and for a single oral dose of triazolam (0.125 mg) were obtained the day before initiation of treatment with modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo (28 days). A second dose of triazolam was administered with the final dose of modafinil, and pharmacokinetic profiling was repeated. RESULTS: The modafinil treatment group had a marked decrease in maximum observed plasma concentrations and areas under the plasma concentration-time curve for triazolam relative to placebo, with a much smaller decrease in these parameters for ethinyl estradiol. The half-life of triazolam was also decreased, but the half-life of ethinyl estradiol did not appear to be affected by treatment with modafinil. CONCLUSION: Modafinil induced CYP3A4/5 activity in humans in vivo, suggesting that there is potential for metabolic drug-drug interactions between modafinil and substrates of CYP3A4/5. However, the induction appeared to be more gastrointestinal than hepatic in nature. Therefore significant metabolic drug-drug interactions are most likely to occur with compounds (such as triazolam) that undergo significant gastrointestinal CYP3A4/5-mediated first-pass metabolism.[1]References
- Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. Robertson, P., Hellriegel, E.T., Arora, S., Nelson, M. Clin. Pharmacol. Ther. (2002) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
