Metabolism of megestrol acetate and related progesterone analogues by liver preparations in vitro |
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Authors: | B. A. Cooke and D. K. Vallance |
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Affiliation: | Department of Biological Research, The British Drug Houses Ltd., Borough Road, Godalming, Surrey |
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Abstract: | 1. The rates of metabolism of megestrol acetate, 17alpha-acetoxy-6alpha-methylprogesterone, 6alpha-methylprogesterone, 17alpha-acetoxyprogesterone and progesterone by liver microsome-supernatant fractions from female rats and rabbits have been compared. 2. Introduction of the 6alpha-methyl group into the progesterone molecule markedly decreased the metabolism by liver microsome-supernatant preparations in the rat but not in the rabbit. When 17alpha-acetoxy was the substituting group, metabolism was diminished in the rabbit but not in the rat preparations. Introduction of both the 6alpha-methyl and 17alpha-acetoxy groups into the progesterone molecule markedly decreased the rate of metabolism by liver microsome-supernatant preparations of both species. The Delta(6)-bond in megestrol acetate confers additional resistance to metabolism by rabbit-liver preparations. 3. It is proposed that the observed inhibition of metabolism by these substituents in the progesterone molecule partly or wholly explains the enhanced activity of megestrol acetate. |
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