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 (TxB2 production endpoint). Meloxicam was partially selective in emus (IC50 COX-1:COX-2 = 9.1:1). At the current empirical dose (0.5 mg/kg/24 hr), plasma meloxicam concentration is above IC50 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.

Relating neuromuscular control to functional anatomy of limb muscles in extant archosaurs.

Electromyography (EMG) is used to understand muscle activity patterns in animals. Understanding how much variation exists in muscle activity patterns in homologous muscles across animal clades during similar behaviours is important for evaluating the evolution of muscle functions and neuromuscular control. We compared muscle activity across a range of archosaurian species and appendicular muscles, including how these EMG patterns varied across ontogeny and phylogeny, to reconstruct the evolutionary history of archosaurian muscle activation during locomotion. EMG electrodes were implanted into the muscles of turkeys, pheasants, quail, guineafowl, emus (three age classes), tinamous and juvenile Nile crocodiles across 13 different appendicular muscles. Subjects walked and ran at a range of speeds both overground and on treadmills during EMG recordings. Anatomically similar muscles such as the lateral gastrocnemius exhibited similar EMG patterns at similar relative speeds across all birds. In the crocodiles, the EMG signals closely matched previously published data for alligators. The timing of lateral gastrocnemius activation was relatively later within a stride cycle for crocodiles compared to birds. This difference may relate to the coordinated knee extension and ankle plantarflexion timing across the swing-stance transition in Crocodylia, unlike in birds where there is knee flexion and ankle dorsiflexion across swing-stance. No significant effects were found across the species for ontogeny, or between treadmill and overground locomotion. Our findings strengthen the inference that some muscle EMG patterns remained conservative throughout Archosauria: for example, digital flexors retained similar stance phase activity and M. pectoralis remained an 'anti-gravity' muscle. However, some avian hindlimb muscles evolved divergent activations in tandem with functional changes such as bipedalism and more crouched postures, especially M. iliotrochantericus caudalis switching from swing to stance phase activity and M. iliofibularis adding a novel stance phase burst of activity.