Safety of ponazuril 15% oral paste in horses

Ponazuril, a triazine-derivative compound, is proposed as a treatment for equine protozoal myeloencephalitis caused by Sarcocystis neurona. Ponazuril 15% oral paste was administered to 24 horses at 0, 10, or 30 mg/kg body weight for either 28 or 56 days, representing zero, two, and six times the proposed dosage rate and one and two times the recommended duration of treatment, respectively. Serum chemistry analysis, coagulation profile, and hematology measurements were performed weekly and necropsy evaluations, including histopathology, were conducted for all animals at the end of the study. Minimal reactions were noted during the treatment period. Soft stools were observed in four of 16 treated horses and three of eight control animals. Serum blood urea nitrogen levels increased and serum sodium levels decreased in horses receiving 10 mg/kg; however, these changes were not associated with number of days on treatment and no value for either variable was outside the normal reference range. No signs of colic were observed in any treated animal during the study. At necropsy, uterine edema was noted in three of the four mares treated with ponazuril at 30 mg/kg. No other treatment-related postmortem or histologic abnormalities were identified in any of the horses. These findings suggest that ponazuril has minimal toxic potential when dosed at levels up to six times the recommended clinical dosage and for one or two times longer than the recommended duration.