Pre-clinical toxicology of nitazoxanide--a new antiparasitic compound.

The acute and subchronic toxicological effects of nitazoxanide were investigated at levels near and in excess of the therapeutic dose in rats, mice, dogs and cats. Single oral gavage doses of 0.625-10 g per kg body weight were administered to rats and mice. Single oral doses of 1-10 g per kg body weight were administered in capsules to dogs and cats. Acute oral LD50 values were greater than 10 g kg-1 in rats, dogs and cats, and 1.4 g kg-1 in mice. Systemic toxicity was evaluated in a repeated dose study in rats at doses of 50, 150 and 450 mg per kg per day for 14 weeks. The highest dose group exhibited intense salivation, increased liver and spleen weight, and decreased thymus weights. Variances between control and treated organ weights were not confirmed by histopathological evaluation. Nitazoxanide was negative when tested in the Ames Salmonella assay using five tester strains with and without metabolic activation at levels from 1 to 100 mg per plate. The drug was also shown to be non-irritating in a test for eye irritation potential.