Differences in the Pregnancy-Terminating Effectiveness of an LH-RH Analogue by Subcutaneous, Vaginal, Rectal, and Nasal Routes in Rats

Abstract

A long-acting analogue of LH-RH, des-Gly¹⁰-[D-Leu⁶]-LH-RH-ethylamide (TAP-144), was administered once or twice on day 9 of pregnancy by subcutaneous, vaginal, rectal, and nasal routes to rats; the pregnancy-terminating effectiveness of these routes was determined on day 14.
When rats were given a single dose of TAP-144, the ED₅₀, value was 1.2μg/100g body weight by the vaginal route, the effectiveness being 752 and 1, 221 times higher than those by the subcutaneous and rectal routes, respectively. Nasal administration was not effective in terminating pregnancy even at a high dose of 2, 000μg/100g body weight. The addition of a surfactant (BL-9) did not increase the effectiveness by the rectal route.
When TAP-144 was administered twice a day, the effectivess was markedly increased by every route. The ED₅₀ values were 0.32μg/100g body weight/time by the subcutaneous route, which was comparable to that of the vaginal route, 14.2μg of the rectal route, and 84.6μg of the nasal route. The addition of the surfactant increased the effectiveness 26 times by the nasal route but not by the rectal route.
The pregnancy-terminating effect of TAP-144 was reversed by treatment with progesterone.