Pharmacokinetics of amitriptyline and its demethylated and hydroxylated metabolites in streptozocin-induced diabetic rats

Plasma and brain levels of amitriptyline (AMI), its demethylated and hydroxylated metabolites were determined after acute IP administration of AMI (20 mg/kg) in streptozocin-induced diabetic Sprague-Dawley rats. Results showed 1. 1. in plasma: rapid AMI absorption, but slow elimination; 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. 2. in brain: the proportions of AMI and nortriptyline were 9.5- and 2.6-fold higher respectively, than those of whole hydroxylated metabolites, which represented 7.4% of the total amount.