Pharmacokinetics of Diclazuril in the Plasma and Cerebrospinal Fluid of Healthy Adult Horses After a Single Oral Dose Administered as a Pelleted Topdressing

Equine protozoal myeloencephalitis can cause acute infections with rapid onset of neurologic signs, necessitating immediate empiric therapy with antiprotozoal medication. The objective of the study was to identify when concentrations of diclazuril reached the MIC of Sarcocystis neurona in CSF (1 ng/mL) of healthy adult horses after a single oral dose. Six healthy adult horses were used. Blood and CSF were collected from indwelling intravenous jugular catheters and intrathecal catheters in the lumbosacral space prior to drug administration and then at 1-, 4-, 8-, 12-, 16-, 24-, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h post-administration of a 1 mg/kg dose of pelleted diclazuril administered by mouth in 8 oz of sweet feed. Samples were centrifuged then plasma and CSF supernatant were separated and frozen at -80°C until analysis. Diclazuril concentrations were analyzed with a liquid chromatography-mass spectrometer assay developed specifically for this study. Plasma concentrations of diclazuril peaked at 48 h with a mean concentration of 395.6 ± 109.4 ng/mL. CSF concentrations of diclazuril peaked at 24 h (mean concentration 9.0 ± 5.4 ng/mL) but achieved the MIC of S. neurona 12 h after administration (mean concentration 2.6 ± 1.8 ng/mL) and remained above MIC for the duration of the sampling period. In conclusion, pelleted diclazuril at 1 mg/kg reaches concentrations in the CSF above the MIC for S. neurona in healthy horses 12 h after a single oral dose.