COMPARATIVE PHARMACOKINETICS OF COUMARIN ANTICOAGULANTS .42. EFFECT OF PHENOBARBITAL ON SYSTEMIC AVAILABILITY OF ORALLY-ADMINISTERED DICUMAROL IN RATS WITH LIGATED BILE-DUCTS

被引：2

作者：

CROW, JW ^{[1
]}

GIBALDI, M ^{[1
]}

LEVY, G ^{[1
]}

机构：

[1] SUNY BUFFALO,SCH PHARM,DEPT PHARMACEUT,AMHERST,NY 14260

来源：

JOURNAL OF PHARMACEUTICAL SCIENCES | 1979年 / 68卷 / 10期

关键词：

Anticoagulants—dicumarol; systemic availability; effect of phenobarbital in bile duct‐ligated rats; Bile duct—ligation; effect on rats; dicumarol systemic availability; phenobarbital; Dicumarol—phenobarbital effect on systemic availability in bile duct‐ligated rats; Drug interactions—phenobarbital effect on dicumarol systemic availability in bile duct‐ligated rats; Phenobarbital—effect on dicumarol systemic availability in bile duct‐ligated rats;

D O I：

10.1002/jps.2600681030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The purpose of this investigation was to determine if the previously demonstrated inhibitory effect of phenobarbital treatment on the systemic availability of orally administered dicumarol in rats is related to the known effect of phenobarbital on bile output. It was found that phenobarbital had no apparent effect on the systemic availability of an aqueous dicumarol suspension in rats with ligated bile ducts. Compared to results obtained previously on normal rats, bile duct‐ligated rats absorbed and eliminated dicumarol much more slowly and absorbed much less of the anticoagulant. On the other hand, the relative inductive effect of phenobarbital treatment on dicumarol elimination was similar in normal and in bile duct‐ligated animals. The latter exhibited substantial serum transaminase elevations, indicative of liver damage presumably secondary to cholestasis. These results demonstrate that a drug‐drug interaction can depend markedly on the pathophysiological status of the animals. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company

引用

页码：1309 / 1312

页数：4

共 10 条

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