Comparison of amitriptyline metabolism in hepatocytes from streptozocin-induced diabetic rats and from non-diabetic rats

被引：2
|
作者：
Coudore, F [1 ]
Besson, A [1 ]
Shrivastava, R [1 ]
Chevalier, A [1 ]
Eschalier, A [1 ]
Lavarenne, J [1 ]
Massingham, R [1 ]
Fialip, J [1 ]
机构：
[1] CERM,RIOM LABS,CTR RECH & DEV,RIOM,FRANCE
来源：
CELL BIOLOGY AND TOXICOLOGY | 1997年 / 13卷 / 02期
关键词：
diabetes; rat; cell culture; antidepressant; kinetics; biotransformation;
D O I：
10.1023/B:CBTO.0000010398.63757.4c
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Biotransformation of amitriptyline (AMI) was studied at different intervals in freshly isolated hepatocytes from healthy or streptozocin-induced diabetic rats in order to investigate the influence of the diabetic state. Levels of free and conjugated AMI, demethylated and hydroxylated metabolites, were assessed by HPLC analysis. In hepatocytes isolated from diabetic rats, AMI was less completely metabolized and the demethylation reaction became more important than in nondiabetic rat hepatocytes. Although the proportions of hydroxylated metabolites decreased in diabetic rats, it always remained predominant. Furthermore, glucuronidation of metabolites was greater, especially for (Z)-10-hydroxynortriptyline in diabetic animals.
引用
收藏
页码：131 / 137
页数：7
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