Pharmacokinetic modeling and simulation of etodolac following single oral administration in dogs.

Etodolac is a nonsteroidal anti-inflammatory drug with selective cyclooxygenase-2 inhibition to treat pain and inflammation associated with osteoarthritis in humans and dogs. The aim of the study was to investigate the pharmacokinetics of etodolac following single oral administration of 200 mg to 10 healthy beagle dogs. The plasma concentrations of etodolac were detected using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted using the noncompartmental method and modeling approaches. Etodolac was rapidly absorbed (Tmax  = 0.85 h, Ka  = 1.49 h-1 ) and slowly eliminated (T1/2  = 39.55 h) following oral administration to the dogs. A two-compartment pharmacokinetic model with first-order absorption and elimination rate constants was successfully explained for the pharmacokinetic aspects of etodolac in dogs. From a Monte Carlo simulation (1000 repetitions), the accumulation index and AUCτ at steady state were predicted as 1.60 [90% confidence intervals (CI), 1.24-2.81] and 408.18 ng·hr/mL [90% CI, 271.26-590.58 ng·hr/mL], respectively. This study will help to enact a more accurate optimal dosing regimen of etodolac in dogs with osteoarthritis, and may be useful in developing a novel formulation of etodolac for human in the future.