TY - JOUR
T1 - An ethinyl estradiol-levonorgestrel containing oral contraceptive does not alter cytochrome p4502c9 in vivo activity
AU - Cherala, Ganesh
AU - Pearson, Jacob
AU - Maslen, Cheryl
AU - Edelman, Alison
PY - 2014/3
Y1 - 2014/3
N2 - 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 coadminister levonorgestrel-containing oral contraceptives and CYP2C9 substrates, which include a wide array of drugs.
AB - 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 coadminister levonorgestrel-containing oral contraceptives and CYP2C9 substrates, which include a wide array of drugs.
UR - http://www.scopus.com/inward/record.url?scp=84893856196&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893856196&partnerID=8YFLogxK
U2 - 10.1124/dmd.113.054346
DO - 10.1124/dmd.113.054346
M3 - Article
C2 - 24368832
AN - SCOPUS:84893856196
SN - 0090-9556
VL - 42
SP - 323
EP - 325
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 3
ER -