van Amsterdam P H, Overmars H, Scherpenisse P M, de Bree H
Eur J Drug Metab Pharmacokinet. 1980;5(3):173-84. doi: 10.1007/BF03189462.
An investigation of the urinary metabolites of the oral progestational agent dydrogesterone in healthy women of childbearing age is reported. The drug was administered in 3H-labelled form and the urine of the first 8 h, containing on average 38% of the radioactivity administered, was used as the source of the metabolites. It was fortified with urine collected during the first 8 h of a similar study with nonlabelled dydrogesterone. After enzymatic hydrolysis of conjugated metabolites, 43 different chemical species were isolated by means of extraction, followed by column and thin layer chromatography. Three of these metabolites, constituting about 70% of the urinary radioactivity, were positively identified as 20 alpha-hydroxy-9 beta, 10 alpha-pregna-4, 6-diene-3-one (52%), 21-hydroxy-9 beta, 10 alpha-pregna-4, 6-diene-3, 20-dione (18%) and 16 alpha-hydroxy-9 beta, 10 alpha-4, 6-diene-3, 20-dione (1%). Of the remainder, 20 (13%) were tentatively characterized as various products of oxidative attack, all probably having the 4, 6-diene-3-one configuration intact. It is concluded that the 4, 6-diene-3-one configuration is metabolically stable in combination with the 9 beta, 10 alpha configuration. This finding may explain why dydrogesterone, in contrast no progesterone, is orally effective, and lacks estrogenic properties.
本文报道了对育龄健康女性口服孕激素地屈孕酮尿液代谢物的研究。该药物以3H标记形式给药，给药后前8小时的尿液用作代谢物来源，其平均含有给药放射性的38%。用未标记地屈孕酮的类似研究中前8小时收集的尿液对其进行强化。对结合代谢物进行酶水解后，通过萃取，然后柱色谱和薄层色谱法分离出43种不同的化学物质。其中三种代谢物，约占尿液放射性的70%，被明确鉴定为20α-羟基-9β，10α-孕甾-4,6-二烯-3-酮（52%）、21-羟基-9β，10α-孕甾-4,6-二烯-3,20-二酮（18%）和16α-羟基-9β，10α-孕甾-4,6-二烯-3,20-二酮（1%）。其余20种（13%）被初步鉴定为氧化攻击的各种产物，所有这些产物可能都保持4,6-二烯-3-酮构型完整。结论是，4,6-二烯-3-酮构型与9β，10α构型结合时在代谢上是稳定的。这一发现可能解释了为什么地屈孕酮与孕酮不同，口服有效且缺乏雌激素特性。
