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Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics.
Abstract: Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral data consistent with the presence of diclazuril. After a single oral dose of diclazuril at 2.5 g/450 kg (as 500 g Clinacox), plasma samples from four horses showed good plasma concentrations of diclazuril which peaked at 1.077 +/- 0.174 microg/mL (mean +/- SEM) with an apparent plasma half-life of about 43 h. When this dose of Clinacox was administered daily for 21 days to two horses, mean steady state plasma concentrations of 7-9 microg/mL were attained. Steady-state levels in the CSF ranged between 100 and 250 ng/mL. There was no detectable parent diclazuril in the urine samples of dosed horses by HPLC or by routine postrace thin layer chromatography (TLC). These results show that diclazuril is absorbed after oral administration and attains steady-state concentrations in plasma and CSF. The steady state concentrations attained in CSF are more than sufficient to interfere with Sarcocystis neurona, whose proliferation is reportedly 95% inhibited by concentrations of diclazuril as low as 1 ng/mL. These results are therefore entirely consistent with and support the reported clinical efficacy of diclazuril in the treatment of clinical cases of EPM.
Publication Date: 2000-01-29 PubMed ID: 10651466DOI: 10.1046/j.1365-2885.1999.00232.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
- Bioavailability
- Biological Half-Life
- Cerebrospinal Fluid
- Clinical Study
- Disease Treatment
- Drug
- Equine Diseases
- Equine Health
- Equine Protozoal Myeloencephalitis
- High-performance Liquid Chromatography (HPLC)
- Horses
- Oral Administration
- Pharmaceuticals
- Pharmacokinetics
- Plasma
- Protozoa
- Treatment
- Veterinary Medicine
- Veterinary Practice
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research explores and confirms the pharmacokinetics of Diclazuril, a potential treatment for Equine Protozoal Myeloencephalitis (EPM) in horses, showing effective absorption after oral administration and sufficient concentrations to likely inhibit the causal parasite.
Understanding Diclazuril and its Identification
- Diclazuril, an antiprotozoal agent known also as Clinacox, is primarily being considered for treatment of Equine Protozoal Myeloencephalitis (EPM) in horses.
- Using a method called high-pressure liquid chromatography (HPLC), the researchers were able to quantitatively track Diclazuril in equine biological fluids. Also, MS/MS analysis, a technique which helps to identify the compounds present in a sample, yielded data consistent with the presence of Diclazuril.
Pharmacokinetics and Bioavailability of Diclazuril
- In the pharmacokinetic study, a single oral dose of Diclazuril was given to horses where it displayed good levels detected in the plasma. This peaked on average around 1.077 micrograms/mL and appeared to stay in the system with a half-life of 43 hours.
- Continued administration of the drug daily over 21 days resulted in steady plasma concentrations of 7-9 micrograms/mL. Within the cerebrospinal fluid (CSF), the drug maintained steady concentrations between 100 and 250 ng/mL.
- Importantly, this drug could not be detected in the horse’s urine post administration, highlighting the drug’s absorption and likely storage in the body rather than being excreted quickly.
Efficacy against EPM and Conclusions
- EPM is thought to be caused by the parasite Sarcocystis neurona, which is reportedly 95% inhibited by concentrations of Diclazuril as low as 1 ng/mL.
- As the levels of Diclazuril in both plasma and CSF were much higher than this through the oral administration, the researchers suggest it could potentially be a very effective treatment for EPM.
- In conclusion, the researchers found that Diclazuril is effectively absorbed after oral administration and creates steady-state concentrations in both blood plasma and CSF that could potentially inhibit the pathogenic activity of Sarcocystis neurona, thus supporting its clinical efficacy in treating EPM.
Cite This Article
APA
Dirikolu L, Lehner F, Nattrass C, Bentz BG, Woods WE, Carter WG, Karpiesiuk W, Jacobs J, Boyles J, Harkins JD, Granstrom DE, Tobin T.
(2000).
Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics.
J Vet Pharmacol Ther, 22(6), 374-379.
https://doi.org/10.1046/j.1365-2885.1999.00232.x Publication
Researcher Affiliations
- Department of Veterinary Science, The Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington 40546, USA.
MeSH Terms
- Administration, Oral
- Animals
- Biological Availability
- Chromatography, High Pressure Liquid / veterinary
- Coccidiostats / administration & dosage
- Coccidiostats / blood
- Coccidiostats / cerebrospinal fluid
- Coccidiostats / pharmacokinetics
- Female
- Horses / blood
- Horses / cerebrospinal fluid
- Horses / metabolism
- Mass Spectrometry / veterinary
- Nitriles / administration & dosage
- Nitriles / blood
- Nitriles / cerebrospinal fluid
- Nitriles / pharmacokinetics
- Triazines / administration & dosage
- Triazines / blood
- Triazines / cerebrospinal fluid
- Triazines / pharmacokinetics
Citations
This article has been cited 5 times.- Onzere CK, Hulbert M, Sears KP, Williams LBA, Fry LM. Tulathromycin and Diclazuril Lack Efficacy against Theileria haneyi, but Tulathromycin Is Not Associated with Adverse Clinical Effects in Six Treated Adult Horses. Pathogens 2023 Mar 14;12(3).
- Bowden GD, Land KM, O'Connor RM, Fritz HM. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth. Int J Parasitol Drugs Drug Resist 2018 Apr;8(1):137-144.
- Reed SM, Furr M, Howe DK, Johnson AL, MacKay RJ, Morrow JK, Pusterla N, Witonsky S. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention. J Vet Intern Med 2016 Mar-Apr;30(2):491-502.
- Oz HS. Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis. Int J Clin Med 2014 Aug;5(15):921-932.
- Oz HS, Tobin T. Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis. Int J Clin Med 2014 Jan 1;5(3):93-101.
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