Imipramine in dogs: A pharmacokinetic study following oral administration under fasted and fed conditions

Abstract

This study investigates the pharmacokinetics (PK) of imipramine, a tricyclic antidepressant used in human psychiatric disorders and increasingly considered in veterinary medicine. Despite its longstanding use in canines, prior research on imipramine's PK in dogs is lacking. This study aimed to determine the PK of imipramine in dogs in regards to feeding conditions, and to ascertain whether desipramine (active metabolite) is formed or not. In this study, six male Labrador dogs underwent oral administration (1.5 mg/kg) of imipramine tablets (10 mg each; Tofranil®, Novartis) in both fasted and fed conditions. Dogs were randomly allocated to one of two treatment groups, employing an open, single-dose, two-treatment, two-phase, cross-over design, with a washout period of one week. Blood was drawn from the left cephalic vein to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma concentrations were quantified using a validated HPLC method, and the data were analyzed using PKanalix™ software with a non-compartmental approach.

Concentrations of imipramine remained quantifiable up to 1.5 hr after administration under both conditions. Desipramine, in both feeding states, was detectable for a short duration, but not quantifiable. No significant differences were observed in the PK parameters of imipramine between the fasting and fed states. The rapid attainment of maximum concentration (C_max) occurred within 0.25 h, indicating a swift absorption rate. Notably, the terminal half-life in dogs was remarkably short at 0.25 h, prompting a re-evaluation of dosing strategies. Considering the recommended therapeutic plasma concentrations in humans, the administered dose might result in effective levels for a brief period of time. Future research should explore intravenous administration, multiple-dose studies, and metabolic investigations to further elucidate imipramine's PK in dogs.