title: An ethinyl estradiol-levonorgestrel containing oral contraceptive does not alter cytochrome P4502C9 in vivo activity.
abstract: 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 interactions 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 tolbutamide 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 contraception, do not affect the status of the CYP2C9 enzyme. This suggests that it is safe to co-administer levonorgestrel-containing oral contraceptives and CYP2C9 substrates, which include a wide array of drugs.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, Oregon State University/Oregon Health & Science University, Portland, Oregon (G.C., J.P.); and Departments of Molecular and Medical Genetics (C.M.) and Obstetrics and Gynecology (G.C., A.E.), Oregon Health & Science University, Portland, Oregon.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Cherala
authors.forename: Jacob
authors.initials: J
authors.lastname: Pearson
authors.forename: Cheryl
authors.initials: C
authors.lastname: Maslen
authors.forename: Alison
authors.initials: A
authors.lastname: Edelman
mesh_terms: D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D065729:Cytochrome P-450 CYP2C9; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D013379:Substrate Specificity; D014044:Tolbutamide / Q000008:administration & dosage / Q000097:blood; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D014044:Tolbutamide; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases