Originally published on TheHorse.com
Veterinarians have been treating equine protozoal myeloencephalitis (EPM) with ponazuril (Marquis) since the Food and Drug Administration approved the antiprotozoal in 2001 but, as with any pharmaceutical approach to disease, fine-tuning an effective treatment protocol is always a work in progress. In laboratory studies scientists have shown ponazuril must reach a particular concentration in the cerebrospinal fluid (CSF) to kill Sarcocystis neurona (a causative agent of EPM), so clinicians wondered if they could be more efficient by starting with a stronger loading dose.
Stephen Reed, DVM, Dipl. ACVIM, of Rood & Riddle Equine Hospital, and research colleagues re-examined the pharmacokinetics (how the drug levels are processed and maintained in the body) of ponazuril in the horse. He presented the results at the 2012 Annual Convention of the American Association of Equine Practitioners, Dec. 1-5in Anaheim, Calif.
The team administered ponazuril in eight adult horses, giving each a single oral dose at the labeled 5 mg/kg rate. They obtained serum and CSF samples from the horses over the next eight days
The researchers then calculated that with this dose, it would take approximately one week to reach a steady-state concentration of the ponazuril level that's lethal to S. neurona--100 micrograms/L. They extrapolated from this model to conclude that a 15 mg/kg loading dose would produce steady-state concentrations immediately.
Reed said ponazuril is very safe; veterinarians conducting safety trials used up to six times the label dose without ill effect. Using the loading-dose method, the 15mg/kg loading dose would be followed by the standard 28-day treatment prescribed on the label. In his talk, Reed speculated that achieving therapeutic levels of ponazuril in the CSF sooner could minimize S. neurona-caused damage.
He acknowledged that some veterinarians have raised concerns that a quick kill might cause more severe clinical signs in the horse, but practitioners at Rood & Riddle have used the loading-dose protocol for some time since the completion of the trial without any adverse effects.
Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.