Pharmacokinetics of a low dose and FDA-labeled dose of diclazuril administered orally as a pelleted topdressing in adult horses.

The research explores the pharmacokinetics of the FDA-approved dose of diclazuril in adult horses, comparing it to a lower dosage. The study aimed to understand the drug’s behavior in the body to establish the best dosage level to achieve the required drug concentration for optimal efficacy.

Study Design and Methodology

• The experiment was conducted in two phases. In each phase, six healthy adult horses were administered a single oral dose of diclazuril pellets. The first phase used a lower dose of 0.5 mg/kg, whereas the second used the FDA-approved dose of 1 mg/kg.
• Blood was collected from the horses before administering the drug and then at regular intervals for up to 168 hours. This was done to analyze the drug’s absorption, distribution, and elimination over time.
• To ensure the drug reached a steady-state concentration, a daily oral dose was administered for 10 days after the last blood collection. The Cerebrospinal fluid (CSF) and blood samples were collected after the 9th and 10th doses, respectively, to determine the steady-state concentration of the drug.
• After a four-week washout period, the procedure was repeated with the FDA-approved dosage.

Data Analysis

• The plasma and CSF samples taken from the horses were analyzed using high-pressure liquid chromatography, a technique used to separate, identify, and quantify each component in a mixture.
• A one-compartment pharmacokinetic model was used to analyze and interpret the data obtained from a single administration of the drug.
• A noncompartmental analysis was employed for steady-state analysis to allow an understanding of the drug’s pharmacokinetics without making assumptions about the physical meaning of various pharmacokinetic parameters.

Study Findings

• The CSF concentration of diclazuril post-administration of the lower dose was found to be slightly higher than after administering the FDA-approved dosage. However, the difference was not statistically significant, suggesting both doses achieved comparable inhibitory concentrations in the CSF.
• Substantial accumulation of the drug occurred in the plasma at steady-state after the 10th dose, regardless of the dosage amount. This indicates that both the approved and lower doses managed to maintain similar steady-state plasma concentrations.
• The data suggest that both the FDA-approved dose and the lower dose of diclazuril pellets can inhibit Sarcocystis neurona, a protozoan parasite, in cell cultures. This indicates that even a lower dosage could possibly be sufficient to achieve the therapeutic benefits of this medication in horses.