Abstract: Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (Protazil) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five individual diclazuril doses were administered at weekly intervals to 8 adult horses. Blood was collected via venipuncture immediately before (trough concentration) and 10 hours after (peak concentration) each diclazuril administration. Following the fifth dose, additional blood samples were collected every 24 hours after the peak blood collection for 7 days. All plasma samples were analyzed by high-pressure liquid chromatography. The pharmacokinetic analysis was performed using a nonlinear mixed effects model. The mean population-derived peak concentration was 264 ng/mL and the mean terminal half-life was 3.6 days. Thus, the oral administration of an FDA-labeled dose of diclazuril to healthy horses once a week was able to produce steady-state plasma drug concentrations known to inhibit S. neurona in vitro.
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This study explores the effects of administering a regular FDA-approved dose of diclazuril, a prophylactic drug, to adult horses, with the aim of finding steady-state concentrations that can hinder the growth of Sarcocystis neurona, a parasite causing Equine protozoal myeloencephalitis (EPM), a debilitating neurological disease in horses.
Objective and Methodology
The research aimed to determine the efficacy and reliability of using the FDA-approved dosage (1mg/kg of 1.56% diclazuril, also known as Protazil) on a weekly basis. The objective was to achieve steady plasma concentrations of the drug that could consistently inhibit S. neurona in healthy adults horses.
Eight adult horses were administered five separate weekly doses of the drug. Before and 10 hours after each drug administration, blood samples were taken via venipuncture. After the last (fifth) dose, additional blood samples were taken every 24 hours for a week.
The plasma samples obtained through this process were analyzed using high-pressure liquid chromatography, and the pharmacokinetic analysis was completed through a nonlinear mixed effects model.
Findings and Conclusion
The results indicated that the averages of the peak plasma concentration of the drug were 264 ng/mL and the terminal half-life was 3.6 days.
The important conclusion derived from this study is that the weekly oral dose of FDA-approved diclazuril in healthy horses is able to maintain steady plasma drug concentrations. These concentrations are known to inhibit growth of S. neurona in lab conditions.
Therefore, on the basis of the study’s findings, it can potentially be assumed that the prescribed dosage strategy is effective in offering prophylactic protection against EPM in horses.
Implication of the Study
This research is particularly significant as it is geared towards fighting Equine protozoal myeloencephalitis, a major neurological disease commonly found in horses in America, especially the younger, performance-focused ones.
The study provides evidence and confidence in the preventive medication strategies for EPM by establishing the efficacy and regular dosing requirements of diclazuril for adult horses.
Such findings can help in better management of EPM, by providing an effective prophylactic treatment strategy.
Cite This Article
APA
Pusterla N, Vaala W, Bain FT, Chappell DE, Craig B, Schneider C, Barnett DC, Gaughan E, Papich MG.
(2022).
Pharmacokinetics of a FDA-labeled dose of diclazuril administered orally once weekly to adult horses.
J Equine Vet Sci, 120, 104183.
https://doi.org/10.1016/j.jevs.2022.104183
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA. Electronic address: npusterla@ucdavis.edu.
Vaala, Wendy
Merck Animal Health, Madison, NJ, USA.
Bain, Fairfield T
Merck Animal Health, Madison, NJ, USA.
Chappell, Duane E
Merck Animal Health, Madison, NJ, USA.
Craig, Bryant
Merck Animal Health, Madison, NJ, USA.
Schneider, Chrissie
Merck Animal Health, Madison, NJ, USA.
Barnett, D Craig
Merck Animal Health, Madison, NJ, USA.
Gaughan, Earl
Merck Animal Health, Madison, NJ, USA.
Papich, Mark G
College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
MeSH Terms
Horses
Animals
Coccidiostats / pharmacology
Coccidiostats / therapeutic use
Seroepidemiologic Studies
Sarcocystis
Nitriles / pharmacology
Nitriles / therapeutic use
Conflict of Interest Statement
Conflict of Interest The authors have the following declaration of interest: Drs. Nicola Pusterla, and Mark Papich have no conflict of interest to declare. Drs. Wendy Vaala, Fairfield T. Bain, Duane E. Chappell, Bryant Craig, Chrissie Schneider, D. Craig Barnett, Earl Gaughan work for Merck Animal Health.