Steroidal ethers - metabolism of enol ethers of delta-4-3-ketosteroids.
Enol ethers of delta-4-3-ketosteroids were found in our laboratories to present peculiar biological properties, several of them showing an increased potency, by oral administration, with respect to the parent steroids. This prompted us to investigate the metabolism in vivo of some representatives of this class; preliminary results on this matter have been already published. In the framework of these researches, the metabolism of the orally active progesterone 3-cyclopentyl enol ether (Quingestrone), was studied after oral administration to healthy subjects. The urinary metabolites were found to be identical with the well-known progesterone metabolites, but a different ratio between the individual metabolites was observed. The main feature of Quingestrone metabolism is the increased ration between 5alpha and 5beta metabolites in comparison with that observed after progesterone. This aspect is discussed, taking into account similar results obtained in the study of the metabolism of enol ethers from delta-4-3-ketoandrostanes. On this basis, some hypotheses on the general metabolic pathways of 3-enol ethers of delta-4-3-ketosteroids are formulated. Other features of the metabolism of these compounds are discussed, such as the effect of the vehicle on their absorption, and the delayed excretion of their metabolites.(FULL TEXT)