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Serum concentration patterns of an LHRH agonist, gonadotrophins and sex steroids after subcutaneous, vaginal, rectal and nasal administration of the agonist to pregnant rats.

A highly potent LHRH agonist, des-Gly10-[D-Leu6]-LHRH-ethylamide (TAP-144), was administered by subcutaneous, vaginal, rectal and nasal routes to pregnant rats on Day 10. After subcutaneous administration, almost all the TAP-144 was rapidly absorbed and eliminated. After vaginal administration, the fraction of the dose that reached the systemic circulation, the F value, was very high but the rate of absorption was very low; consequently there was a low peak level and persistence of serum level. After rectal administration, the F value was very low and the rate of absorption was lower than that by the subcutaneous route; consequently the terminal phase half-life was between those of the subcutaneous and vaginal routes. After nasal administration, the F value was also very low but the rate of absorption was enormously high and there was a rapid decrease in serum concentration. The pregnancy-terminating effectiveness of the peptide by these routes of administration was not proportional to the transient high concentrations of the peptide but attributable to its persistence in the serum. Serum LH and FSH concentrations after TAP-144 administration showed similar patterns with the different routes but the peak concentration of LH after vaginal administration was higher than that after other routes. Serum levels of progesterone and oestradiol-17 beta showed small peaks within 2 h after TAP-144 was administered by any route and fluctuated thereafter but the level dropped only in the rats given a dose of TAP-144 that was 100% effective in terminating pregnancy.