Metabolism of [4-14c]lynestrenol in Man

Abstract

SUMMARY After the administration of [4-14C]lynestrenol (17α-ethynyl-19-nor-androst-4-en-17β-ol) to 7 human subjects 31·–57·6% of the dose, whether administered orally or i.v., was excreted in the urine within 5 days. The biological half-life of radioactivity was 26·5 hr. After acid and enzymatic hydrolysis, 58·7 and 45·6% respectively of the urinary radioactivity was extractable. About 10% of the urinary metabolites were excreted as sulphate conjugates. A mean value of 1·75% of the administered dose was converted to phenolic compounds. The metabolites in the free fraction and enzymehydrolysed extract of urine were almost entirely polar compounds, whereas 70% of the metabolites in the sulphate fraction were much less polar. The chromatographic evidence showed that hydroxylation of lynestrenol must have occurred at two points in the molecule. Plasma radioactivity decreased more rapidly than after administration of norethisterone.

Identification of the human cytochrome P450 enzymes involved in the in vitro biotransformation of lynestrenol and norethindrone

“…In the metabolite identification phase it was found that lynestrenol undergoes rather rapid metabolism to form norethindrone, which was the principal metabolite observed in the incubations with human liver microsomes. This finding is in accordance with earlier observations [2,3]. No other metabolites were formed directly from lynestrenol except norethindrone, which was further biotransformed via hydroxylation and double bond formation (or alternatively via cleavage of water from hydroxymetabolite) to four metabolites.…”

“…Lynestrenol is a prodrug, which is converted to norethindrone both in vitro [2] and in vivo [3,4]. Parent drug lacks progesto- Fig.…”

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

“…There does not appear to be any information about aromatization of compounds lacking a 3-oxo group. However, Kamyab, Fotherby & Klopper (1968) showed that labelled lynoestrenol gave rise to 1'75% phenolic substances in the urine in man. Paper chromatography indicated the presence of two hydroxyl groups in the molecule.…”

Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug

“…The amount of radioactivity in the freelyextractable fraction in urine was 14-28% of the total daily urinary radioactivity in this investigation. When the figures reported for other progestagens with a 17ct-ethinyl-19-nor-structure (Layne et al 1963;Kamyab et al 1968;Fotherby et al 1968;Hendeles et al 1972;Sisenwine et al 1973) are considered, it is evident that the free steroid frac¬ tion is very high in the case of Org 2969.…”