Metabolism of megestrol acetate and related progesterone analogues by liver preparations in vitro.
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.
D000818:Animals; D002854:Chromatography, Paper; D003276:Contraceptives, Oral / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology; D008535:Megestrol / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011372:Progestins / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D003276:Contraceptives, Oral; D011372:Progestins; D009249:NADP; D008535:Megestrol