Biological efficacy and plasma norethisterone levels of orally administered norethisterone enanthate in rat and hamster.

ABSTRACT

Norethisterone enanthate (NET-En) is a well known intramuscular contraceptive drug. The long acting nature of this preparation when administered orally was evaluated in female rats and hamsters using fertility inhibition test and from the plasma levels of norethisterone (NET). An oral dose of 20-60 mg NET-En was administered to random groups of six female rats and hamsters and were mated after five and ten days with males of proven fertility. The fertility inhibition rate was determined from vaginal delivery. A dose-dependent reduction in fertility was seen in rats 5 days after oral administration of NET-En. This effect was found to be less pronounced and not significant 10 days after administration of similar doses of NET-En. In hamsters, a similar but less pronounced effect was noted. The decrease in fertility was significant only at the 60 mg dose. The plasma levels of NET estimated by RIA over a period of 15 days, in a different set of treated rats, suggested rapid absorption of NET-En within a day, and drug concentration decreased slowly, the levels on the 4th day ranged from 0.9-2.3 with the 10 mg and 1.0-4.0 ng/ml with the 20 mg dose. Detection of adequate levels of NET in plasma during the estrous cycle in rats, and the fertility inhibition observed in female rats and at higher doses in hamsters, suggest that NET-En is orally active.