Dosage Requirements for Orally Administered Phenylbutazone in African and Asian Elephants (Loxodonta africana and Elephas maximus)
Phenylbutazone is a non-steroidal anti-inflammatory drug that works through inhibition of the arachidonic acid cascade to decrease production of prostaglandins and thromboxane. It has been used in elephants to treat inflammatory conditions like arthritis with empirical dosages ranging between 1–2 mg/kg every 24 hours. However, metabolic scaling calculations are unreliable due to the large difference in body size of elephants compared to other species, and potential negative side effects from use of phenylbutazone can include gastrointestinal ulceration and inhibition of T4 to T3 conversion. To determine safe and therapeutic dosing regimens for phenylbutazone in elephants, 17 animals held in captivity in North America were used in this study.
Pharmacokinetic parameters of phenylbutazone were determined in 10 African (Loxodonta africana) and seven Asian (Elephas maximus) elephants after single-dose oral administrations of 2, 3, and 4 mg/kg doses as well as multiple-dose administrations. There were significant differences in pharmacokinetic values between elephant species for clearance, terminal half-life, and mean residence time. For example, clearance for 2 mg/kg dosages was 27.9 versus 6.5 ml/hour/kg for African and Asian elephants, respectively, concurrent with mean residence times of 27.5 versus 66.4 hours. Asian elephants also showed a double peak in plasma concentrations versus time, suggesting enterohepatic recycling of phenylbutazone in Asian but not African elephants. Different treatment regimens are recommended. Based on the results of this study, we recommend Asian elephants receive 3 mg/kg every 48 hours and African elephants receive 2 mg/kg every 24 hours.
We thank the elephant keepers and staff at the following organizations for collecting blood samples for this study: Kansas City Zoo, Riddle’s Elephant Sanctuary, the Bowmanville Zoo, Seneca Park Zoo, Wild Things, Inc., and Oregon Zoo. The Morris Animal Foundation provided funding for this research.