Pretomanid: which tox species, and why?

“GLP-compliant repeat-dose toxicity studies of 14 days, 3 months, and 6 months duration were conducted in rats and studies of 2 weeks, 3 months, and 9 months duration were conducted in cynomolgus monkeys.”

“Rats and monkeys were chosen as target species for the toxicology studies. These species showed extensive metabolism and it has been shown that all human circulating extractable metabolites detected following a single oral dose of pretomanid were formed in the relevant toxicological animal species”

“Oral administration of pretomanid to cynomolgus monkeys for 9 months at doses of 0, 25, 50, and 100 mg/kg/day was generally well tolerated.”

“GLP-compliant repeat-dose toxicity studies of 14 days, 3 months, and 6 months duration were conducted in rats and studies of 2 weeks, 3 months, and 9 months duration were conducted in cynomolgus monkeys.”

“fertility and pre- and post-natal developmental studies in rats; embryo-fetal developmental studies in rats and rabbits”

“No carcinogenic potential was revealed in a 6-month study in transgenic mice where this metabolite was produced. In a 2-year study in rats, there was no evidence of carcinogenic risk.”

“Oral administration of pretomanid to cynomolgus monkeys for 9 months at doses of 0, 25, 50, and 100 mg/kg/day was generally well tolerated.”