Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.
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Robertson P Jr, Hellriegel ET, Arora S, Nelson M
Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.
Clin Pharmacol Ther. 2002 Jan;71(1):46-56.
- PubMed ID
- 11823757 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Armodafinil Cytochrome P450 3A4 Protein Humans UnknownInducerDetails Armodafinil Cytochrome P450 3A5 Protein Humans UnknownInducerDetails Modafinil Cytochrome P450 3A4 Protein Humans UnknownSubstrateInducerDetails Modafinil Cytochrome P450 3A5 Protein Humans NoSubstrateInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbemaciclibModafinil The metabolism of Abemaciclib can be increased when combined with Modafinil. AbemaciclibArmodafinil The metabolism of Abemaciclib can be increased when combined with Armodafinil. AbrocitinibArmodafinil The metabolism of Abrocitinib can be decreased when combined with Armodafinil. AbrocitinibModafinil The metabolism of Abrocitinib can be decreased when combined with Modafinil. AcalabrutinibModafinil The metabolism of Acalabrutinib can be increased when combined with Modafinil. AcalabrutinibArmodafinil The metabolism of Acalabrutinib can be increased when combined with Armodafinil. AcenocoumarolModafinil The metabolism of Acenocoumarol can be increased when combined with Modafinil. AcenocoumarolArmodafinil The metabolism of Acenocoumarol can be increased when combined with Armodafinil. AlbendazoleModafinil The metabolism of Albendazole can be decreased when combined with Modafinil. AlbendazoleArmodafinil The metabolism of Albendazole can be decreased when combined with Armodafinil. 
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