Short Communication An Ethinyl Estradiol-Levonorgestrel Containing Oral Contraceptive Does Not Alter Cytochrome P4502C9 In Vivo Activity

Oral contraceptives have been in wide use for more than 50 years. Levonorgestrel, a commonly employed progestin component of combined oral contraceptives, was implicated in drug–drug interac-tions mediated via CYP2C9. Although in vitro studies refuted this interaction, there are no confirmatory in vivo studies. In the current study, we examined the phenotypic status of CYP2C9 using low-dose (125 mg) tolbutamide before and after oral contraceptive use in reproductive age women. Blood was collected 24 hours after the tolbutamide oral dose was administered, plasma was isolated, and tolbutamide concentration (C24) was measured using liquid chromatography–mass spectrometry. The natural logarithm of tolbu-tamide C24, a metric for CYP2C9 phenotype, was found to be equivalent (within 80%–125 % equivalency boundaries) before and after oral contraceptive use. In conclusion, levonorgestrel-containing oral contraceptives, the most commonly used form of oral contracep-tion, do not affect the status of the CYP2C9 enzyme. This suggests that it is safe to coadminister levonorgestrel-containing oral contra-ceptives and CYP2C9 substrates, which include a wide array of drugs