Perioperative pharmacokinetics and pharmacodynamics of meloxicam in emus (Dromaius novaehollandiae) of different age groups using nonlinear mixed effect modelling.

Meloxicam is a widely used nonsteroidal anti-inflammatory drug in avian species. However, variability in pharmacokinetic (PK) and pharmacodynamic (PD) parameters in birds warrants species-specific studies for dose and dosing interval optimization. We performed a perioperative PK study of meloxicam (0.5 mg/kg, intravenously) on emus of three different age groups: 3 chicks (5 weeks old, 3.5 kg), 4 juveniles (26 weeks old, 18.8 kg) and 6 adults (66 weeks old, 38.8 kg). A two-compartment population PK model including weight as a significant covariate on clearance and central volume of distribution (V1) best fitted the data. The typical values (20 kg bird) for clearance and V1 were 0.54 L/kg/h and 0.095 L/kg. Both parameters significantly decreased with increasing weight/age. Meloxicam potency and selectivity for COX-1 and COX-2 were measured in whole blood assays (TxB production endpoint). Meloxicam was partially selective in emus (IC COX-1:COX-2 = 9.1:1). At the current empirical dose (0.5 mg/kg/24 hr), plasma meloxicam concentration is above IC of COX-2 for only 2 hr. PK/PD predicted dose required for 80% COX-2 inhibition over 24 hr were 3.4, 1.4 and 0.95 L/kg/day in chicks, juveniles and adult emus, respectively. The safety, therapeutic efficacy and practicality of modifying the daily dose or dose interval should be considered for dose recommendations in emus.