Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3-4 days.
Abstract: The purpose of this study was to determine if a low dose of diclazuril (0.5mg/kg of 1.56% diclazuril pellets) given to six healthy adult horses every 3-4 days for a total of five administrations would achieve steady-state plasma concentrations known to be inhibitory to Sarcocystis neurona and Neospora caninum. Blood was collected via venipuncture immediately before (trough concentrations) and 10h after (peak concentrations) each diclazuril administration and analysed by high-pressure liquid chromatography. The mean population-derived peak concentration was 0.284μg/mL and the mean terminal half-life was 1.6 days, but with a large variation. Thus, low dose diclazuril pellets produce steady-state plasma drug concentrations known to inhibit S. neurona (0.001μg/mL) and N. caninum (0.1μg/mL).
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication Date: 2018-11-08 PubMed ID: 30503548DOI: 10.1016/j.tvjl.2018.10.009Google Scholar: Lookup
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Summary
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The research study examines if a small dosage of diclazuril, administered to horses every 3-4 days, could achieve a steady plasma concentration that is known to inhibit the growth of diseases caused by Sarcocystis neurona and Neospora caninum.
Objective of the Research
- The aim of this study was to understand if administering a low dose of diclazuril at periodic intervals could lead to achieving a steady plasma concentration enough to inhibit two specific diseases – Sarcocystis neurona and Neospora caninum, both of which are harmful to horses.
Details of the Study
- In order to measure the pharmacokinetics of diclazuril, the researchers experimentally administered low doses of diclazuril (0.5 mg/kg of 1.56% diclazuril pellets) to six healthy adult horses every 3-4 days.
- The experiment extended over five administrations in order to gauge the drug’s capacity to reach steady-state plasma concentrations within this interval.
Methodology and Results
- To monitor the drug levels, blood was collected from the horses before (baseline concentrations) and 10 hours after (peak concentrations) each diclazuril administration.
- The analysis of the plasma samples was executed by high-pressure liquid chromatography, a technique often applied for separating, identifying, and quantifying each component in a mixture.
- The mean population-derived peak concentration was reportedly 0.284μg/mL and the mean terminal half-life was 1.6 days.
- The study discovered the presence of large variations in the terminal half-life, hinting at the individual variations in the horses’ metabolism and absorption of the drug.
Conclusions
- From the results, it was concluded that the low dose of diclazuril pellets can indeed produce stable plasma drug concentrations known to prevent the proliferation of S. neurona (0.001μg/mL) and N. caninum (0.1μg/mL).
- This implies that a strategic and controlled administration of diclazuril could be potent in preventing these horse diseases caused by these two specific parasites.
Cite This Article
APA
Hunyadi L, Papich MG, Pusterla N.
(2018).
Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3-4 days.
Vet J, 242, 74-76.
https://doi.org/10.1016/j.tvjl.2018.10.009 Publication
Researcher Affiliations
- Equine Sports Medicine and Surgery, 2991 West Interstate 20, South Frontage Road, Weatherford, TX 76087, USA.
- College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA.
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA. Electronic address: npusterla@ucdavis.edu.
MeSH Terms
- Administration, Oral
- Animals
- Coccidiostats / administration & dosage
- Coccidiostats / blood
- Coccidiostats / pharmacokinetics
- Drug Administration Schedule
- Female
- Horses / blood
- Horses / metabolism
- Male
- Nitriles / administration & dosage
- Nitriles / blood
- Nitriles / pharmacokinetics
- Triazines / administration & dosage
- Triazines / blood
- Triazines / pharmacokinetics
Citations
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