Pharmacokinetic Analysis of Two Different Doses of Duloxetine Following Oral Administration in Dogs

Abstract

Duloxetine is a potent and balanced dual inhibitor of serotonin and norepinephrine reuptake that is being investigated for the treatment of depression and urinary incontinence. The purpose of this study was to investigate the pharmacokinetic properties of duloxetine in 20 beagle dogs following a single oral administration of a 30- or 60-mg enteric-coated pellet in a capsule (Cymbalta). Following the administration of 30 or 60 mg of Cymbalta to 20 beagle dogs, the plasma concentration of duloxetine was measured using LC-MS/MS. Pharmacokinetic parameters were analyzed using both noncompartmental and compartmental approaches. The values of C max and AUC increased in proportion to the dose of duloxetine. The one compartment model with first-order absorption and a lag time was used successfully for pharmacokinetic analysis of duloxetine following a single oral administration of Cymbalta 30 mg or 60 mg. The studies described here are the first to report the pharmacokinetics of oral duloxetine in dogs, and these findings provide important information for pharmaceutical formulation research of duloxetine using dogs.