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

Authors
  • Coudoré, F
  • Besson, A
  • Shrivastava, R
  • Chevalier, A
  • Eschalier, A
  • Lavarenne, J
  • Massingham, R
  • Fialip, J
Type
Published Article
Journal
Cell biology and toxicology
Publication Date
Feb 01, 1997
Volume
13
Issue
2
Pages
131–137
Identifiers
PMID: 9049103
Source
Medline
License
Unknown

Abstract

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 non-diabetic 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.

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