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Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats.

作者信息

Schmoldt A

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1978 Dec;305(3):261-3. doi: 10.1007/BF00498820.

DOI:10.1007/BF00498820
PMID:740054
Abstract

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-beta-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.

摘要

相似文献

1
Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats.
Naunyn Schmiedebergs Arch Pharmacol. 1978 Dec;305(3):261-3. doi: 10.1007/BF00498820.
2
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Biochem Pharmacol. 1972 May 15;21(10):1449-55. doi: 10.1016/0006-2952(72)90369-3.

引用本文的文献

1
Cleavage of digoxigenin digitoxosides by rat liver microsomes.
Eur J Drug Metab Pharmacokinet. 1980;5(4):225-32. doi: 10.1007/BF03189468.
2
Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):226-33. doi: 10.1007/BF00165306.

本文引用的文献

1
THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE.肝微粒体的一氧化碳结合色素。I. 其血红蛋白性质的证据。
J Biol Chem. 1964 Jul;239:2370-8.
2
Diphenylhydantoin metabolism by rat liver microsomes and some of the effects of drug or chemical pretreatment on diphenylhydantoin metabolism by rat liver microsomal preparations.
J Pharmacol Exp Ther. 1971 Jan;176(1):11-26.
3
The effect of spironolactone on drug metabolism by hepatic microsomes.螺内酯对肝微粒体药物代谢的影响。
J Pharmacol Exp Ther. 1971 Mar;176(3):766-71.
4
Cleavage by beta-glucuronidase of the water-soluble metabolites of digitoxin excreted in the bile of control and spironolactone-pretreated rats.对照大鼠和螺内酯预处理大鼠胆汁中排泄的洋地黄毒苷水溶性代谢产物经β-葡萄糖醛酸酶的裂解作用
Toxicol Appl Pharmacol. 1974 Mar;27(3):641-7. doi: 10.1016/0041-008x(74)90043-x.
5
Enhanced biliary excretion of digitoxin following sprionolactone as it relates to the prevention of digitoxin toxicity.螺内酯后洋地黄毒苷胆汁排泄增加及其与洋地黄毒苷毒性预防的关系。
Res Commun Chem Pathol Pharmacol. 1973 Jan;5(1):99-108.
6
Biliary excretion of 3 H-digitoxin: modification by bile salts and phenobarbital.3H-地高辛的胆汁排泄：胆汁盐和苯巴比妥的影响
J Lab Clin Med. 1973 Feb;81(2):241-51.
7
Effect of microsomal enzyme inducers on the biliary excretion of cardiac glycosides.微粒体酶诱导剂对强心苷胆汁排泄的影响。
J Pharmacol Exp Ther. 1974 Nov;191(2):201-11.
8
Interactions of spironolactone with hepatic microsomal drug-metabolizing enzyme systems.
Biochem Pharmacol. 1971 Aug;20(8):1991-2000. doi: 10.1016/0006-2952(71)90398-4.
9
Proceedings: Comparison of liver enzyme induction by polychlorinated biphenyls (PCB) and phenobarbital studied for digitoxin metabolism in rats.论文集：多氯联苯（PCB）和苯巴比妥对大鼠洋地黄毒苷代谢的肝酶诱导作用比较研究
Naunyn Schmiedebergs Arch Pharmacol. 1974;282(Suppl):suppl 282:R85.
10
Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats.螺内酯预处理对大鼠中洋地黄毒苷药代动力学及代谢的影响。
Naunyn Schmiedebergs Arch Pharmacol. 1975;287(2):129-39. doi: 10.1007/BF00510445.