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Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration

B. KIMBLE

L. A. BLACK

K. M. LI

P. VALTCHEV,

S. GILCHRIST,

A. GILLETT,

D. P. HIGGINS,

M. B. KROCKENBERGER,

M. GOVENDIR

Faculty of Veterinary Science, The University of Sydney

Faculty of Pharmacy, The University of Sydney

The Australia Zoo Wildlife Hospital, Beerwah, Qld

ABSTRACT:

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44  0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz) of 0.72  0.22 L/kg and a volume of distribution at steady state (Vss) of 0.22  0.12 L/kg. Median plasma terminal half-life (t1/2) was 1.19 h (range 0.71–1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (Cmax 0.013  0.001 and 0.014  0.001 lg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 lg/mL] between 4–8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.