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Lack of Effect of Rosiglitazone on the Pharmacokinetics of Oral Contraceptives in Healthy Female Volunteers
Author(s) -
Inglis Anne Marie L.,
Miller Ann K.,
Culkin Kathleen Thompson,
Finnerty Dana,
Patterson Scott D.,
Jorkasky Diane K.,
Freed Martin I.
Publication year - 2001
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700122010456
Subject(s) - ethinylestradiol , pharmacokinetics , rosiglitazone , medicine , crossover study , placebo , gestodene , endocrinology , pharmacology , population , receptor , alternative medicine , environmental health , pathology , family planning , research methodology
The effect of rosiglitazone (Avandia® [BRL 49653C]) on the pharmacokinetics of ethinylestmdiol 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, doubleblind, 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(024) 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.