Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration.

Abstract

Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2mg/kg was administered to healthy adult rhinoceros (n=33) housed at six North American zoological institutions. Each rhinoceros had up to four blood samples collected under voluntary behavioural restraint at up to four predetermined time points (0, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 30 and 48h). Drug analysis was performed by high-performance liquid chromatography. The population pharmacokinetic parameters were calculated with nonlinear mixed-effects modelling, and analysis showed a peak concentration (CMAX ) of 3.8µg/ml at 1.8h and an elimination half-life of 9h. The concentrations achieved were similar to what has been reported for horses and were within the half maximal effective concentration for horses for at least 10h. A multi-dose trial in five rhinoceros receiving 2mg/kg orally once daily for five days found mild accumulation at a predicted factor of 1.2. This study represents the first pharmacokinetic data of phenylbutazone in any rhinoceros species.