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Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus)

Robert P. Hunter MS, PhD1, Ramiro Isaza MS, DVM, DACZM2, and David E. Koch MS3
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  • 1 Zoological Pharmacology Laboratory, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5802.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5802.
  • | 3 Zoological Pharmacology Laboratory, Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5802.

Abstract

Objective—To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus).

Animals—5 adult Asian elephants.

Procedure—Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis.

Results—The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration.

Conclusion and Clinical Relevance—Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined. (Am J Vet Res 2003;64:109–114)

Abstract

Objective—To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus).

Animals—5 adult Asian elephants.

Procedure—Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis.

Results—The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration.

Conclusion and Clinical Relevance—Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined. (Am J Vet Res 2003;64:109–114)