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

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.

Effects of inorganic mercury on reproductive performance of mice.

Effects of mercuric chloride (MC) on the reproductive performance of mice were evaluated. Both male and female mice were divided into four groups that were subsequently exposed to 0.00, 0.25, 0.50, and 1.00 mg/kg/day of MC, respectively. At the end of pre-mating dosing, males were paired with females receiving the same dose. Dosing continued for males throughout mating, while dosing in females continued throughout mating, gestation, and lactation. The males were necropsied at the conclusion of mating and the females were necropsied at the conclusion of lactation. Fertility indices, parturition, gestation, live birth litter size, survival indices, and implantation efficiency were recorded. Subsequently, these data were statistically analyzed. Fertility and survival indices were significantly reduced in the treated groups. Exposure of mice to MC did not affect their litter size. No evidence of mercury induced target organ toxicity was seen in either the clinical pathology parameters or histomorphologic evaluations. However, in MC treated females, ovary weights were significantly different from the control. There were no histomorphologic or clinical pathology effects induced by MC. These results suggested that oral exposure to 0.25-1.00 mg/kg/day of MC produced adverse effects on the reproductive performance of mice in the absence of overt mercury toxicity.