Optimum time for administration of indomethacin to inhibit ovulation in the rabbit

The antiinflammatory agent, indomethacin, inhibits ovulation in mammals by interfering with the synthesis of prostaglandins in preovulatory follicles. To determine the optimum time to administer this inhibitor, indomethacin was given at specific intervals from 10 h before, and up to 9 h after, the ovulatory process had been initiated by hCG (50 I.U./kg). The drug dosage ranged from 1.25 mg/kg to 40 mg/kg. The optimum time to give indomethacin was at 7-8 h after hCG (i.e., 2-3 h before expected rupture of the follicle) at which time the minimum effective dose was 2.5 mg/kg. Since a significant elevation in prostaglandin synthesis occurs as early as 3-5 h after hCG stimulation of rabbit follicles (1), these results reveal that nonsteroidal antiinflammatory agents can interrupt the ovulatory process even after the follicle has begun producing substantial amounts of prostaglandins. The data suggest that prostaglandins need to be produced continuously in the follicle up to the time of actual rupture or else that indomethacin is interfering with some other aspect of the ovulatory process which transpires after the elevation of prostaglandins.