Pharmacokinetics of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus)

Abstract

OBJECTIVES To characterize the pharmacokinetics of a single oral dose (6 mg/kg) of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus) and to characterize any clinicopathologic effects with this medication and dose. ANIMALS Six healthy, 4-month-old New Zealand White rabbits (3 male, 3 female). PROCEDURES Before drug administration, clinicopathologic samples were collected for baseline data (CBC, serum biochemical analyses, and urinalysis including urine protein-to-creatinine ratio). All 6 rabbits received a single oral dose (6 mg/kg) of mavacoxib. Clinicopathologic samples were collected at set time intervals to compare with the base-line. Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using non-compartmental methods. RESULTS After a single oral dose, the maximum plasma concentration (Cmax; mean, range) was 854 (713–1040) ng/mL, the time to Cmax (tmax) was 0.36 (0.17–0.50) days, the area under the curve from 0 to the last measured time point (AUC0-last) was 2000 (1765–2307) days*ng/mL, the terminal half-life (t1/2) was 1.63 (1.30–2.26) days, and the terminal rate constant (λz) was 0.42 (0.31–0.53) days. All results for CBCs, serum biochemical analyses, urinalyses, and urine protein-to-creatinine ratios remained within published normal reference intervals. CLINICAL RELEVANCE This study determined that plasma concentrations reached target levels of 400 ng/mL for 48 hours in 3/6 rabbits at 6 mg/kg PO. In the remaining 3/6 rabbits, the plasma concentrations were 343–389 ng/mL at 48 hours, which is below the target concentration. Further research is needed to make a dosing recommendation, including a pharma-codynamic study and investigating pharmacokinetics at different doses and multiple doses.