New therapeutic approaches for equine protozoal myeloencephalitis: pharmacokinetics of diclazuril sodium salts in horses

摘要

Diclazuril is a triazine-based antiprotozoal agent which may have clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, the use of the sodium salt diclazuril to increase the apparent bioavailability of diclazuril for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases is described. In this study, diclazuril sodium salt was synthesized and administered to horses as diclazuril sodium salt formulations. The absorption, distribution, and clearance of diclazuril sodium salt in the horse are described. Diclazuril was rapidly absorbed, with peak plasma concentrations occurring at 8-24 hours following an oral mucosal administration of diclazuril sodium salt. The mean oral bioavailability of diclazuril as Clinacox was 9.5% relative to oral mucosal administration of diclazuril sodium salt. Additionally, diclazuril in DMSO administered orally was 50% less bioavailable than diclazuril sodium salt following an oral mucosal administration. It was also shown that diclazuril sodium salt has the potential to be used as a feed additive for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases.