PHARMACOKINETICS OF ORALLY ADMINISTERED IBUPROFEN IN AFRICAN AND ASIAN ELEPHANTS (LOXODONTA AFRICANA AND ELEPHAS MAXIMUS)

Abstract

The pharmacokinetic parameters of S( ) and R(−) ibuprofen were determined in 20 elephants after oral administration of preliminary 4-, 5-, and 6-mg/kg doses of racemic ibuprofen. Following administration of 4 mg/kg ibuprofen, serum concentrations of ibuprofen peaked at 5 hr at 3.9 ± 2.07 μg/ml R(−) and 10.65 ± 5.64 μg/ml S( ) (mean ± SD) in African elephants (Loxodonta africana) and at 3 hr at 5.14 ± 1.39 μg/ml R(−) and 13.77 ± 3.75 μg/ ml S( ) in Asian elephants (Elephas maximus), respectively. Six-milligram/kilogram dosages resulted in peak serum concentrations of 5.91 ± 2.17 μg/ml R(−) and 14.82 ± 9.71 μg/ml S( ) in African elephants, and 5.72 ± 1.60 μg/ ml R(−) and 18.32 ± 10.35 μg/ml S( ) in Asian elephants. Ibuprofen was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.2–2.4 hr R(−) and 4.5–5.1 hr S( ) in African elephants and 2.4–2.9 hr R(−) and 5.9–7.7 hr S( ) in Asian elephants. Serum concentrations of R(−) ibuprofen were undetectable at 24 hr, whereas S( ) ibuprofen decreased to below 5 μg/ml 24 hr postadministration in all elephants. The volume of distribution was estimated to be between 322 and 356 ml/kg R(−) and 133 and 173 ml/kg S( ) in Asian elephants and 360–431 ml/kg R(−) and 179–207 ml/kg S( ) in African elephants. Steady-state serum concentrations of ibuprofen ranged from 2.2 to 10.5 μg/ml R(−) and 5.5 to 32.0 μg/ml S( ) (mean: 5.17 ± 0.7 R(−) and 13.95 ± 0.9 S( ) μg/ ml in African elephants and 5.0 ± 1.09 μg/ml R(−) and 14.1 ± 2.8 μg/ml S( ) in Asian elephants). Racemic ibuprofen administered at 6 mg/kg/12 hr for Asian elephants and at 7 mg/kg/12 hr for African elephants results in therapeutic serum concentrations of this antiinflammatory agent.