Metabolites of lynestrenol acetate in the bile of rats after intravenous administration; a comparison with lynestrenol.
Some aspects of the metabolism of lynestrenol acetate, an orally active contraceptive compound, were studied in female rats.  Lynestrenol acetate is stable in gastric and intestinal juice in vitro.  After intravenous administration of lynestrenol acetate and lynestrenol with a -14C label in the nucleus approximately 40% of the administered radioactivity was excreted in the bile within 90 min.  After administration of lynestrenol acetate labelled in the ester group, 6% of the radioactivity was found in the bile.  This means that the greater part of the lynestrenol acetate had lost its acetate group during the process of metabolism.  There was an important difference between the autoradiograms of the thin layer patterns of post-hydrolysis extracts after administration of [4-14C]lynestrenol acetate and those after administration of [1'-14C]lynestrenol acetate and [4-14C]lynestrenol: the major metabolite of [4-14C]lynestrenol acetate did not appear on the autoradiograms of [1'--14C]lynestrenol acetate and [4-14C]lynestrenol.  This indicates that lynestrenol acetate was altered in the nucleus in the presence of the acetate group.  The acetate group itself was removed, either when the alterations took place, or after it had been completed.  The results of IR, NMR and mass spectrometry analysis indicate the introduction of a 15alpha hydroxyl group.  Results of gas-liquid chromatography and thin layer chromatography indicate that a second important metabolic is 19-nor-17alpha-pregn-20-yne-3alpha, 17beta-diol.  The main conclusions are: 1. A part of the lynestrenol acetate is metabolized and excreted in the bile, the acetate group still being present.  2. Lynestrenol acetate is to some extent metabolized via another pathway than lynestrenol.  This indicates that esterification of a steroid can lead to deviation from the metabolic pathway of the free original steroid.
D000085:Acetates / Q000008:administration & dosage / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D006914:Hydroxysteroids / Q000096:biosynthesis; D008234:Lynestrenol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013058:Mass Spectrometry; D009650:Norpregnanes / Q000096:biosynthesis; D051381:Rats
D000085:Acetates; D006914:Hydroxysteroids; D009650:Norpregnanes; D008234:Lynestrenol