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The metabolism in humans of synthetic progestational compounds

Following the administration to humans of [4-14C] norethisterone and [4-14C] lynestrenol, 54% and 43% of the radioactivity was excreted in urine, mostly within two days. The plasma level of radioactivity was higher in the case of norethisterone than that of lynestrenol and remained in the circulation for a longer period. The urinary metabolites of the steroids were studied, and a considerable metabolism of the compounds occurred in the body. Most of the urinary metabolites carried the ethynyl side chain and were polar compounds, probably hydroxylated in more than two positions. Possible conversion of lynestrenol to norethisterone prior to further metabolism is discussed. Following the administration of [4-14C] norethisterone to rabbits, 45% of the radioactivity was excreted in urine and 2.7% in faeces during seven days. Tissue concentration of radioactivity was highest at 5 hr. following the injection and had decreased appreciably by 24 hr. Appreciable concentrations.of radioactivity were detected in liver, bile, intestine and kidney. Uterus seemed to retain the radioactivity, suggesting a possible binding of the steroid metabolites. Considerable metabolism of norethisterone occurred in rabbits, the metabolites being mostly polar compounds. Little metabolism of the ethynyl grouping occurred. The specificity of the method of Fotherby and Love (1960) for the estimation of pregnanetriol excretion in pregnancy is examined. The excretion of pregnanetriol during pregnancy was measured in 15 subjects. The pattern of excretion was different from that of pregnanediol and in one half of the subjects studied there was a rise in the excretion of pregnanetriol during the last trimester of pregnancy. Following progesterone administration, the pregnanetriol excretion was affected in only one of five subjects. Three steroids which contaminated the pregnanetriol fraction of urine during pregnancy were isolated and characterized as 3, 6a-dihydroxy-5β-pregnan-20-one, 3, 16a-dihydroxy-5β-pregnan-20-orie, and 5β-pregnane, 3, 6a, 20β triol. The latter two compounds have not previously been identified in urine.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:623062
Date January 1968
CreatorsKamyab, Soraya
PublisherImperial College London
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://hdl.handle.net/10044/1/15908

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