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 microg/ml R(-) and 10.65 +/- 5.64 microg/ml S(+) (mean +/- SD) in African elephants (Loxodonta africana) and at 3 hr at 5.14 +/- 1.39 microg/ml R(-) and 13.77 +/- 3.75 microg/ml S(+) in Asian elephants (Elephas maximus), respectively. Six-milligram/kilogram dosages resulted in peak serum concentrations of 5.91 +/- 2.17 microg/ml R(-) and 14.82 +/- 9.71 microg/ml S(+) in African elephants, and 5.72 +/- 1.60 microg/ml R(-) and 18.32 +/- 10.35 microg/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 microg/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 microg/ml R(-) and 5.5 to 32.0 microg/ml S(+) (mean: 5.17 +/- 0.7 R(-) and 13.95 +/- 0.9 S(+) microg/ml in African elephants and 5.0 +/- 1.09 microg/ml R(-) and 14.1 +/- 2.8 microg/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.

Zoo elephant research: contributions to conservation of captive and free‐ranging species

“…Drugs to treat non‐specific disease manifestations have focused on non‐steroidal anti‐inflammatories (NSAIDs), and phenylbutazone and flunixin meglumine are most commonly prescribed (Kottwitz et al ., ). Pharmacokinetic studies conducted with NSAIDs in elephants (Table ) include ibuprofen (Bechert & Christensen, ), ketoprofen (Hunter et al ., ), phenylbutazone (Bechert et al ., ), and trials with flunixin meglumine and firocoxib are currently under way. Another pharmacokinetic study was completed with butorphanol, a morphinan‐type synthetic agonist–antagonist opioid also used for analgesia (Tana et al ., ).…”

Elephants, Mobility and Captivity: What Can These Mighty and Majestic Animals Teach Us About Joint Health and Osteoarthritis?

“…Studies have examined the pharmacokinetics of orally administered phenylbutazone in African and Asian elephants and the evidence suggests that different treatment regimens should be used for each species, based on size and weight [37]. Similar studies have established the optimal dosage for using ketoprofen [38] and ibuprofen [39] in elephants. However, these NSAIDs can be highly toxic to the gastrointestinal tract in humans and in large animals such as horses and elephants, causing general toxicity, colitis and inhibition of mucosal barrier healing [40].…”

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“…While online and published formularies exist, there is an extremely limited number of scientific studies performed on the pharmacokinetics of analgesics in elephants. 1,2,5,9,10,15,16 To date, there are no specific pharmacokinetic studies available in any species of rhinoceros to support dosing regimens for drugs used for pain management. Published studies 8,9,12,13 of opioids administered to rhinoceros having focused on administration for sedation and general anesthesia, not analgesia.…”