Pharmacokinetics of R(–) and S(+) carprofen after administration of racemic carprofen in donkeys and horses

Katrina L. Mealey Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164.

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Nora S. Matthews Departments of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.

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Kenneth E. Peck Departments of Texas Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.

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Melissa L. Burchfield

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Brad S. Bennett

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Tex S. Taylor Departments of Large Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.

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Abstract

Objective—To compare plasma disposition of the R(–) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses.

Animals—5 clinically normal donkeys and 3 clinically normal horses.

Procedure—Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentration-time curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables.

Results—In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(–) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(–) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (ClT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and ClT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys.

Conclusions and Clinical Relevance—Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys. (Am J Vet Res 2004;65:1479–1482)

Abstract

Objective—To compare plasma disposition of the R(–) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses.

Animals—5 clinically normal donkeys and 3 clinically normal horses.

Procedure—Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentration-time curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables.

Results—In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(–) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(–) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (ClT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and ClT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys.

Conclusions and Clinical Relevance—Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys. (Am J Vet Res 2004;65:1479–1482)

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