Pharmacokinetics of ponazuril after oral administration to healthy llamas (Lama glama)

Maria E. Prado Department of Animal Science, Institute of Agriculture, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Josiah T. Ryman Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 37163.

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Melanie J. Boileau Center for Veterinary Health Sciences, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

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Tomas Martin-Jimenez Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

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Bernd Meibohm Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 37163.

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Abstract

Objective—To determine the pharmacokinetics after oral administration of a single dose of ponazuril to healthy llamas.

Animals—6 healthy adult llamas.

Procedures—Ponazuril (20 mg/kg) was administered once orally to 6 llamas (day 0). Blood samples were obtained on days 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 21, 28, 35, 42, and 49. Serum ponazuril concentrations were determined by use of a validated reverse-phase high-performance liquid chromatography assay with UV absorbance detection. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis.

Results—Mean ± SD area under the serum concentration–time curve was 7,516 ± 2,750 h•mg/L, maximum serum ponazuril concentration was 23.6 ± 6.0 mg/L, and the elimination half-life was 135.5 ± 16.7 hours. Serum concentration of ponazuril peaked at 84 hours (range, 48 to 120 hours) after administration and gradually decreased but remained detectable for up to 35 days after administration. No adverse effects were observed during the study period.

Conclusions and Clinical Relevance—The rate and extent of absorption following oral administration of a single dose of ponazuril were sufficient to result in potentially effective concentrations, and the drug was tolerated well by llamas. At this dose, ponazuril resulted in serum concentrations that were high enough to be effective against various Apicomplexans on the basis of data for other species. The effective ponazuril concentration that will induce 50% inhibition of parasite growth for Eimeria macusaniensis in camelids is currently unknown.

Abstract

Objective—To determine the pharmacokinetics after oral administration of a single dose of ponazuril to healthy llamas.

Animals—6 healthy adult llamas.

Procedures—Ponazuril (20 mg/kg) was administered once orally to 6 llamas (day 0). Blood samples were obtained on days 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 21, 28, 35, 42, and 49. Serum ponazuril concentrations were determined by use of a validated reverse-phase high-performance liquid chromatography assay with UV absorbance detection. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis.

Results—Mean ± SD area under the serum concentration–time curve was 7,516 ± 2,750 h•mg/L, maximum serum ponazuril concentration was 23.6 ± 6.0 mg/L, and the elimination half-life was 135.5 ± 16.7 hours. Serum concentration of ponazuril peaked at 84 hours (range, 48 to 120 hours) after administration and gradually decreased but remained detectable for up to 35 days after administration. No adverse effects were observed during the study period.

Conclusions and Clinical Relevance—The rate and extent of absorption following oral administration of a single dose of ponazuril were sufficient to result in potentially effective concentrations, and the drug was tolerated well by llamas. At this dose, ponazuril resulted in serum concentrations that were high enough to be effective against various Apicomplexans on the basis of data for other species. The effective ponazuril concentration that will induce 50% inhibition of parasite growth for Eimeria macusaniensis in camelids is currently unknown.

Contributor Notes

Presented in abstract form at the American College of Veterinary Internal Medicine Forum, Anaheim, Calif, June 2010.

The authors thank Dr. Steven A. Ripp for technical assistance.

Address correspondence to Dr. Prado (meprado@utk.edu).
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