PHARMACOKINETICS OF AMITRIPTYLINE AND ITS DEMETHYLATED AND HYDROXYLATED METABOLITES IN STREPTOZOCIN-INDUCED DIABETIC RATS

Plasma and brain levels of amitriptyline (AMI), its demethylated and h ydroxylated metabolites were determined after acute IP administration of AMI (20 mg/kg) in streptozocin-induced diabetic Sprague-Dawley rats . Results showed 1. in plasma: rapid AML absorption, but slow eliminat ion; the proportion of AMI similar to those of the rest of compounds; the proportion of its demethylated metabolite, nortriptyline, 1.8-fold higher than that of 10-hydroxy-nortriptyline. 2. in brain: the propor tions of AMI and nortriptyline were 9.5- and 2.6-fold higher respectiv ely, than those of whole hydroxylated metabolites, which represented 7 .4% of the total amount.