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Pharmacokinetics of a Low Dose of Diclazuril Administered Orally as a Pelleted Top Dressing in Adult Horses
L. Hunyadi, M.G. Papich, N...
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Diclazuril pellets given at a low dose reach plasma and cerebrospinal fluid (CSF) levels known to inhibit Sarcocystis neurona in cell culture. Authors’ addresses: William R. Pritchard Veterinary Medical Teaching Hospital (Hunyadi); Department of Medicine and Epidemiology (Pusterla), University of California, Davis School of Veterinary Medicine, Davis, CA 95616; and College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607 (Papich); e-mail: lmhunyadi@ucdavis.edu.
1. Introduction
The economic impact of EPM in endemic areas on both performance horses and horse breeding industries is substantial. Although various approaches to the prevention of EPM have been investigated, replication of the disease in clinical settings has been elusive. The objective of this study was to determine if the low dose would attain plasma and cerebrospinal fluid (CSF) concentrations that are known to inhibit Sarcocystis neurona in cell culture.
2. Procedures
Six healthy adult horses received 0.5 mg/kg diclazuril pellets as a low dose orally once and plasma samples were collected at regular intervals for 168 h. Daily oral doses were then administered for 10 days. Plasma and CSF were collected once after the 9th dose. After the 10th oral dose, plasma samples were collected at regular intervals for 168 h. The study was repeated with the labeled dose at 1 mg/kg after a 4 week washout period. Plasma and CSF samples were analyzed by high-pressure liquid chromatography. A one-compartment pharmacokinetic model with first-order oral absorption was fitted to the single administration data. Steady-state pharmacokinetics was performed using noncompartmental analysis for steady-state analysis.
3. Results
The mean concentration of diclazuril in the CSF following the low dose was 26 ng/mL whereas the CSF in the labeled dose was 25 ng/mL. The CSF concentrations were only 5 to 6% of the corresponding plasma concentrations and therapeutic plasma concentrations occurred at steady-state after the 10th dose for both doses.
4. Discussion
The results of this study show that diclazuril pellets given at both a low and labeled dose reach plasma and CSF levels known to inhibit Sarcocystis neurona in cell culture after steady-state levels have been reached.
Acknowledgments
Conflict of Interest
The Protazila and pharmacokinetic analysis were sponsored by Merck Animal Health. The horses and CSF analysis were sponsored by University of California Davis. The Authors have no investments or consulting with the sponsors. Two authors are employees of University of California Davis; one is employed by North Carolina State University.
Footnote
a ProtozilTM Merck Animal Health, Summit, NJ 07901-1330.
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Affiliation of the authors at the time of publication
William R. Pritchard Veterinary Medical Teaching Hospital (Hunyadi); Department of Medicine and Epidemiology (Pusterla), University of California, Davis School of Veterinary Medicine, Davis, CA 95616; and College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607 (Papich)
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