醋酸甲地孕酮及相关孕酮类似物在体外肝脏制剂中的代谢

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

Cooke B A, Vallance D K

Biochem J. 1965 Dec;97(3):672-7. doi: 10.1042/bj0970672.

Abstract

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.

摘要

已比较了醋酸甲地孕酮、17α-乙酰氧基-6α-甲基孕酮、6α-甲基孕酮、17α-乙酰氧基孕酮和孕酮在雌性大鼠和兔子肝脏微粒体-上清液组分中的代谢速率。2. 在孕酮分子中引入6α-甲基基团显著降低了大鼠肝脏微粒体-上清液制剂的代谢，但对兔子没有影响。当17α-乙酰氧基作为取代基团时，兔子制剂中的代谢减少，但大鼠制剂中没有。将6α-甲基和17α-乙酰氧基基团都引入孕酮分子中，显著降低了两种动物肝脏微粒体-上清液制剂的代谢速率。醋酸甲地孕酮中的Δ(6)-键赋予其对兔子肝脏制剂代谢的额外抗性。3. 有人提出，孕酮分子中这些取代基对代谢的抑制作用部分或全部解释了醋酸甲地孕酮活性增强的原因。