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SINGLE-DOSE, MULTIPLE-DOSE, AND THERAPEUTIC DRUG MONITORING PHARMACOKINETICS OF FIROCOXIB IN ASIAN ELEPHANTS (ELEPHAS

Jack Kottwitz1, Ursula Bechert2, Crisanta Cruz-Espindola3

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Firocoxib, a COX-2-selective NSAID, is safe and effective for Asian elephants. Oral administration at 0.1 mg/kg every 24 hours, using tablet or paste, is recommended for pain and inflammation management.

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Area of Science:

  • Veterinary Pharmacology
  • Wildlife Health
  • Pharmacokinetics

Background:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are crucial for managing pain and inflammation.
  • Firocoxib offers selective COX-2 inhibition, potentially reducing gastrointestinal side effects.
  • Determining optimal dosing for Asian elephants is essential for effective and safe therapeutic use.

Purpose of the Study:

  • To establish safe and effective oral doses of firocoxib in Asian elephants (Elephas maximus).
  • To evaluate the pharmacokinetics of firocoxib in different formulations (tablet and paste).
  • To assess COX inhibition and identify potential adverse effects of firocoxib.

Main Methods:

  • Single and multidose pharmacokinetic trials were conducted in Asian elephants.
  • Two oral doses (0.01 and 0.1 mg/kg) were initially tested.
  • Firocoxib concentrations, area under the curve (AUC), and half-life (T1/2) were measured.
  • In vitro and ex vivo COX inhibition assays were performed.

Main Results:

  • The 0.1 mg/kg dose demonstrated favorable pharmacokinetic parameters in both tablet and paste formulations.
  • After 8 days of dosing, pharmacokinetic parameters stabilized, indicating predictable drug accumulation.
  • Firocoxib showed preferential inhibition of COX-2, with no observed adverse effects.
  • Mean peak serum concentrations for the 0.1 mg/kg dose were 49 ± 3.3 ng/ml (tablets) and 62 ± 14.8 ng/ml (paste).

Conclusions:

  • Firocoxib at 0.1 mg/kg orally every 24 hours is a suitable dose for Asian elephants.
  • Both tablet and paste formulations are effective, with consistent pharmacokinetic profiles.
  • Firocoxib is a safe and selective COX-2 inhibitor for potential use in treating pain and inflammation in this species.