COMPARISON OF AMITRIPTYLINE METABOLISM IN HEPATOCYTES FROM STREPTOZOCIN-INDUCED DIABETIC RATS AND FROM NONDIABETIC RATS

Biotransformation of amitriptyline (AMI) was studied at different inte rvals in freshly isolated hepatocytes from healthy or streptozocin-ind uced diabetic rats in order to investigate the influence of the diabet ic state. Levels of free and conjugated AMI, demethylated and hydroxyl ated metabolites, were assessed by HPLC analysis. In hepatocytes isola ted from diabetic rats, AMI was less completely metabolized and the de methylation reaction became more important than in nondiabetic rat hep atocytes. Although the proportions of hydroxylated metabolites decreas ed in diabetic rats, it always remained predominant. Furthermore, gluc uronidation of metabolites was greater, especially for (Z)-10-hydroxyn ortriptyline in diabetic animals.