Hildebrand M, Krause W, Kühne G, Hoyer G A
Xenobiotica. 1987 May;17(5):623-34. doi: 10.3109/00498258709043969.
The pharmacokinetics and metabolism of mespirenone were examined in rat and cynomolgus monkey using the tritiated drug. Following i.v. administration, mespirenone exhibited a short half-life and a high plasma clearance; after oral administration the unchanged compound was not detectable. Thus, mespirenone has to be considered a pro-drug. From rat urine three metabolites were isolated by h.p.l.c. and identified by mass spectra and 1H n.m.r., all having retained the 7 alpha-sulphur substituent as a thiomethyl or a sulphinylmethyl group. The 7 alpha-thiomethyl metabolite had a half-life of six hours in rat plasma and its AUC value was 35% of that for total 3H. As this metabolite has marked anti-aldosterone activity, it is an active metabolite that contributes to the pharmacological effect of mespirenone.
使用氚标记的药物在大鼠和食蟹猴中研究了美螺内酯的药代动力学和代谢情况。静脉注射给药后，美螺内酯表现出较短的半衰期和较高的血浆清除率；口服给药后，未检测到原形化合物。因此，美螺内酯必须被视为一种前体药物。通过高效液相色谱法从大鼠尿液中分离出三种代谢物，并通过质谱和1H核磁共振进行鉴定，所有代谢物均保留了7α-硫取代基，为硫甲基或亚磺酰甲基基团。7α-硫甲基代谢物在大鼠血浆中的半衰期为6小时，其曲线下面积值为总3H的35%。由于这种代谢物具有显著的抗醛固酮活性，它是一种活性代谢物，对美螺内酯的药理作用有贡献。
