Pharmacokinetics of Ibuprofen and Phenylbutazone in Elephants Following Oral Administration of Single and Multiple Doses

The pharmacokinetics and dose proportionality of ibuprofen were examined in African and Asian elephants after single dose administration of 4, 5 and 6 mg/kg and on multiple dose administration. Each elephant received all the three doses and plasma ibuprofen concentrations were measured by HPLC. Approximate linearity of ibuprofen pharmacokinetics in elephants was found in the dose ranges of 4-6 mg/kg. On dosing the African elephants at 7 mg/kg and Asian elephants at 6 mg/kg every 12 hours to steady state, the ibuprofen concentrations produced were comparable to therapeutic levels achieved in humans. On comparing the AUC and clearance/F obtained in the single dose study with AUC and clearance determined with multiple dosing to steady state, no significant differences were observed showing ibuprofen followed linear kinetics. The pharmacokinetics and dose proportionality of phenylbutazone were examined in African and Asian elephants after single dose administration of 2, 3 and 4 mg/kg and on multiple dose administration. Each elephant received all the three doses and plasma phenylbutazone concentrations were measured by HPLC. Approximate linearity of phenylbutazone pharmacokinetics in elephants was found in the dose ranges of 2-4 mg/kg. The clearance/F of Asian elephants was significantly lower than African elephants, so proper care should be taken with the dose and dosing frequency in multiple dosing of phenylbutazone for Asian and African elephants. An oral dose of 2 mg/kg every 24 hours was administered to the African elephants and an oral dose of 3 mg/kg every 48 hours was administered to the Asian elephants and the pharmacokinetic parameters were determined at steady state.