Cerebrospinal fluid and serum concentrations of ponazuril in horses.

Abstract: Ponazuril was administered orally to 10 adult horses at 5 mg/kg body weight, once a day for 28 days. Blood was collected once a week from each horse from Days 0 through 35, daily from Days 35 through 42, and on Day 49. Cerebrospinal fluid (CSF) was also collected once a week from Day 0 through Day 49. Concentrations of ponazuril in the serum and CSF were determined, and pharmacokinetic calculations were performed. Ponazuril was readily absorbed following oral administration; and after 7 days of dosing, the serum concentration was 4.33 +/- 1.10 mg/L, and the mean CSF concentration was 0.162 +/- 0.05 mg/L. Cerebrospinal fluid concentration did not vary during the 28 days of dosing and concentrations declined rapidly after cessation of administration on Day 28. The terminal elimination half-life ofponazuril in serum (using Day 28 to 42 results) was 4.3 +/- 0.6 days. Repeated CSF collections from the atlanto-occipital space did not induce changes in the immunoglobulin G index or albumin quotient. It was concluded that oral administration of ponazuril to healthy horses at 5 mg/kg provided concentrations of ponazuril in the CSF that are presumed to be adequate for the treatment of equine protozoal myeloencephalitis (EPM). These results indicate that this dosage rate should be investigated for efficacy against EPM.