Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.

Article Details

Citation

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
DrugEnzymeKindOrganismPharmacological ActionActions
ArmodafinilCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
ArmodafinilCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
ModafinilCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
ModafinilCytochrome P450 3A5ProteinHumans
No
Substrate
Inducer
Details
Drug Interactions
DrugsInteraction
Abemaciclib
Modafinil
The metabolism of Abemaciclib can be increased when combined with Modafinil.
Abemaciclib
Armodafinil
The metabolism of Abemaciclib can be increased when combined with Armodafinil.
Abrocitinib
Armodafinil
The metabolism of Abrocitinib can be decreased when combined with Armodafinil.
Abrocitinib
Modafinil
The metabolism of Abrocitinib can be decreased when combined with Modafinil.
Acalabrutinib
Modafinil
The metabolism of Acalabrutinib can be increased when combined with Modafinil.