Metabolism of megestrol acetate and related progesterone analogues by liver preparations in vitro

摘要

1. The rates of metabolism of megestrol acetate, 17α-acetoxy-6α-methylprogesterone, 6α-methylprogesterone, 17α-acetoxyprogesterone and progesterone by liver microsome–supernatant fractions from female rats and rabbits have been compared. 2. Introduction of the 6α-methyl group into the progesterone molecule markedly decreased the metabolism by liver microsome–supernatant preparations in the rat but not in the rabbit. When 17α-acetoxy was the substituting group, metabolism was diminished in the rabbit but not in the rat preparations. Introduction of both the 6α-methyl and 17α-acetoxy groups into the progesterone molecule markedly decreased the rate of metabolism by liver microsome–supernatant preparations of both species. The Δ⁶-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.