Abstract
Background:
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).
Method:
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.
Results:
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.
Conclusion:
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.
Key words
cymbalta - LC-MS/MS - ADAPT 5 - compartmental analysis - lag time - enteric-coated
capsule
