METABOLISM OF [14C]NORGESTREL IN MAN

Abstract

SUMMARY [14C]Norgestrel was administered to seven human subjects and 43% of dose was excreted in the urine within 5 days; the biological half-life of the radioactivity was 24 hr. Enzymic hydrolysis released only 32% of the the urinary radioactivity and a further 25% was excreted as sulphate conjugates. The metabolites excreted in the urine were much less polar than those following the administration of the related compounds, norethisterone or lynestrenol. The 3αOH,5β and 3βOH,5β isomers of the tetrahydronorgestrel (13β-ethyl-17α-ethynyl-5β-gonane-3α,17β-diol) were isolated from urine and identified by mass spectrometry and thin-layer and gas—liquid chromatography. Plasma radioactivity decreased more rapidly than after the administration of norethisterone and lynestrenol. About 2% of the administered dose was converted to acidic compounds. There was no apparent difference in the rate of excretion of radioactivity or in the metabolites after either oral or intravenous administration of norgestrel.