Studies on the biotransformation of the progestagen dienogest in the rabbit.

Following administration of 14 alpha, 15 alpha-3H-Dienogest (STS 557, 17 alpha-cyanomethyl-17 beta-hydroxy-4, 9-estradien-3-one) to female rabbits, extracts from urine, bile and plasma were separated by means of HPLC. Urinary and biliary metabolites are characterized by patterns of high complexity. From the mass spectra and UV absorption data of the urinary Dienogest metabolites a variety of biotransformation reactions has been derived like: hydroxylation in different positions of the Dienogest molecule, among these the 11-position; reduction of the 3-oxo group to 3-hydroxy; introduction of 2 and 4 hydrogen atoms; aromatization of ring A; transformation of 17 alpha-CH2CN to CH2OH, and formation of compounds with a 5(10), 9(11)-diene structure. Some of these reactions occur simultaneously resulting in a very complicated metabolite spectrum. Possibly the multiple effects of Dienogest established in animals are partially caused by metabolites.