title: Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers.
abstract: The effect of rosiglitazone (Avandia [BRL 49653C]) on the pharmacokinetics of ethinylestradiol and norethindrone was evaluated after repeat dosing of rosiglitazone with an oral contraceptive (OC; Ortho-Novum 1/35 containing norethindrone 1 mg and ethinylestradiol 0.035 mg) in a randomized, double-blind, placebo-controlled crossover study. Thirty-four healthy female volunteers received oral rosiglitazone (RSG) 8 mg + OC or matched placebo (P) + OC daily on days 1 to 14 of a 28-day OC dosing cycle; the alternate regimen was administered during a second cycle. Ethinylestradiol and norethindrone pharmacokinetics were determined from plasma concentrations on day 14. Lack of pharmacokinetic effect was prospectively defined as 90% CI for the point estimate (PE) of the ratio (RSG + OC):(P + OC) contained within a 20% equivalence range for both ethinylestradiol and norethindrone (analyzed by ANOVA). For RSG + OC and P + OC, respectively, mean ethinylestradiol AUC(0-24) was 1126 and 1208 pg.h/mL (PE: 0.92; 90% CI: 0.88-0.97), and mean norethindrone AUC(0-24) was 178 and 171 ng.h/mL (PE: 1.04; 90% CI: 1.00-1.07). Thus, rosiglitazone had no significant effects on the pharmacokinetics of ethinylestradiol or norethindrone. Coadministration of rosiglitazone with OCs does not induce metabolism of these synthetic sex steroids and is not expected to impair the efficacy of OCs or hormone replacement therapy.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Clinical Pharmacology Unit, 51 N. 39th Street, Philadelphia, PA 19104, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Inglis
authors.forename: A K
authors.initials: AK
authors.lastname: Miller
authors.forename: K T
authors.initials: KT
authors.lastname: Culkin
authors.forename: D
authors.initials: D
authors.lastname: Finnerty
authors.forename: S D
authors.initials: SD
authors.lastname: Patterson
authors.forename: D K
authors.initials: DK
authors.lastname: Jorkasky
authors.forename: M I
authors.initials: MI
authors.lastname: Freed
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics* / Q000494:pharmacology; D003280:Contraceptives, Oral, Synthetic / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D045166:Estradiol Congeners / Q000493:pharmacokinetics; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009640:Norethindrone / Q000493:pharmacokinetics*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010919:Placebos; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D045162:Thiazolidinediones
chemical_list: D003277:Contraceptives, Oral, Combined; D003280:Contraceptives, Oral, Synthetic; D045166:Estradiol Congeners; D007004:Hypoglycemic Agents; D010919:Placebos; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004997:Ethinyl Estradiol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D009640:Norethindrone