INCREASED DIGITOXIN CLEAVAGE BY LIVER-MICROSOMES OF SPIRONOLACTONE-PRETREATED RATS

被引：18

作者：

SCHMOLDT, A

机构：

[1] Pharmakologisches Institut der Universität, Hamburg 20, D-2000

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 1978年 / 305卷 / 03期

关键词：

Dehydro-digitoxosides; Digitoxin metabolism; Digitoxoside cleavage; Microsomal monoxygenases; Spironolactone;

D O I：

10.1007/BF00498820

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pretreatment of rats with spironolactone caused an fourfold increased cleavage rate of the sugar chain of digitoxin (dt-3) in vitro yielding digitoxigenin-bis-digitoxoside. This was due to an enhanced, cyt. P450 dependent, formation of 15′-dehydro-dt-3, the intermediate which has to be formed before the terminal sugar can be split off. The second reaction catalysed by microsomal monoxygenases, the 12-β-hydroxylation, was only increased by a factor 2. In contrast to the effects of spironolactone no increase of metabolism could be observed after phenobarbital pretreatment. From our results it may be concluded that the enhanced dt-3 metabolism in vivo is mainly caused by spironolactone inducible monoxygenases which catalyse the oxidation of the terminal sugar. © 1978 Springer-Verlag.

引用

页码：261 / 263

页数：3

共 15 条

[1] CLEAVAGE BY BETA-GLUCURONIDASE OF WATER-SOLUBLE METABOLITES OF DIGITOXIN EXCRETED IN BILE OF CONTROL AND SPIRONOLACTONE-PRETREATED RATS [J].