Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers

The effect of rosiglitazone (Avondia (R) [BRL 49653C]) on the pharmacokinet ics of ethinylestradiol and norethindrone was evaluated after repeat dosing of rosiglitazone with an oral contraceptive (OC; Ortho-Novum (R) 1/35 cont aining norethindrone I mg and ethinylestradiol 0.035 mg) in a randomized, d ouble-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 r egimen was administered during a second cycle. Ethinylestradiol and norethi ndrone pharmacokinetics were determined from plasma concentrations on day 1 4. Lack of pharmacokinetic effect was prospectively defined os 90% CI for t he 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 AU C((0-24)) was 1126 and 1208 pg(.)h/ml (PE: 0.92; 90% CI:0.88-0.970 and mean norethindrone AUC((0-24)) was 178 and 171 ng(.)h/ml (PE: 1.04; 90% CI: 1.0 0-1.07). Thus, rosiglitazone had no significant effects on the pharmacokine tics of ethinylestradiol or norethindrone. Coadministration of rosiglitazon e with OCs does not induce metabolism of these synthetic sex steroids and i s not expected to impair the efficacy of OCs or hormone replacement therapy .