The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives.

OBJECTIVE

This open-label, two-period, crossover study was conducted to evaluate the effect of a single 150 mg dose of fluconazole on the pharmacokinetics of ethinyl estradiol in healthy female subjects.

STUDY DESIGN

Ten subjects regularly taking Ortho-Novum 7/7/7 (Ortho Pharmaceutical, Raritan, N.J.) and 10 subjects regularly taking Triphasil (Wyeth-Ayerst Laboratories, Philadelphia), which contain ethinyl estradiol 35 microg and 30 microg during days 1 to 6, respectively, were randomly assigned to receive a single 150 mg dose of fluconazole 2 hours before the oral contraceptive, on pill day 6 of one of two menstrual cycles. Ethinyl estradiol serum concentrations were measured at baseline and up to 24 hours after oral contraceptive intake. No fluconazole was administered during the other menstrual cycle, which served as the control.

RESULTS

Mean serum concentrations of ethinyl estradiol were increased after fluconazole administration in both oral contraceptive groups. Maximum observed serum concentration and area under the concentration-time curve values were significantly (p < 0.05) greater during the fluconazole regimens (vs regimens without fluconazole) for both oral contraceptive groups and for combined values of the two oral contraceptive groups. The mean time to reach the maximum concentration was not altered by concomitant fluconazole administration.

CONCLUSIONS

These findings suggest that there is a potential for a clinically significant interaction between coadministration of fluconazole and ethinyl estradiol in oral contraceptives.