Plasma levels and progestational activity of levonorgestrel after repeated intravenous and subcutaneous administration in the beagle bitch.

In pharmacological test models providing repeated daily administrations of steroid hormones, differing time courses of the drug level depending upon the pharmacokinetics can be observed often. The present study should make a contribution to the question whether the time course of the drug level can have an influence on the effectiveness of a given dose of a synthetic gestagen. On the basis of existing pharmacokinetic and pharmacodynamic data in the beagle dog, levonorgestrel (LN) was selected as progestogen. LN was administered daily in equal dosages (0.1 mg) over a period of 14 days subcutaneously (s.c.) and intravenously (i.v.). The gestagenic potency of LN was assessed in an established bioassay by the histological evaluation of the endometrial transformation. Whereas the s.c. administration resulted in a low, but almost constant, LN level, high peaks of short duration could be determined after i.v. administration. Following s.c. injection, LN was released only to a degree of 60% in the observation period compared with 100% after i.v. administration. Nevertheless, 0.1 mg LN given s.c. had stronger endometrial effects than 0.1 mg LN given as bolus i.v.