DIRITHROMYCIN INCREASES ETHINYL ESTRADIOL CLEARANCE WITHOUT ALLOWING OVULATION

Objective: To use a novel, sensitive study design to detect a potentia l oral contraceptive (OC) and dirithromycin drug interaction by assess ing the pharmacokinetics of the ethinyl estradiol (E2) component of a common OC and the potential failure of OC effectiveness. Methods: In t his nonblinded study, 20 healthy women using Ortho Novum 7/7/7-28 were selected for a three-OC-cycle study. Baseline measures included E2 an d progesterone serum levels on days 21, 23, 25, and 27 of cycle one an d days 1, 3,5, and 7 of cycle two. During cycle two, 24-hour blood sam pling and radioimmunoassay analysis for ethinyl E2 pharmacokinetics we re performed on day 8 and pelvic ultrasound on day 13. Oral dirithromy cin 500 mg/day for 14 days began on day 21 of cycle 2. After starting dirithromycin, cycle two and three serum E2, progesterone, and serial ethinyl E2 levels and pelvic ultrasound replicated the baseline schedu le. Ovulation was assumed if E2 concentration was greater than 50 pg/m L, progesterone concentration was greater than 3 ng/mL, or if an ovari an cyst greater than 10 mm was present on ultrasound. Results: Pharmac okinetic analysis demonstrated a small (7.6%) but statistically signif icant decrease (P = .03) in the mean ethinyl E2 24-hour area under the curve and an increase in apparent oral clearance. No woman ovulated, based on E2 levels and progesterone concentrations or ultrasound. Conc lusion: Dirithromycin increased the apparent oral clearance of ethinyl E2. The clinical importance of the interaction may be negligible beca use no woman ovulated or had compromised OC effectiveness in this smal l series.