Safety pharmacology and toxicology of a novel nitroimidazooxazole antitubercular agent in SD rat and Beagle dogs - PubMed
6 hours ago
- #Antitubercular
- #Preclinical Safety
- #Pharmacokinetics
- Development of JBD0131, a novel nitroimidazooxazole antitubercular agent.
- Comprehensive preclinical evaluation in SD rats and Beagle dogs showed good tolerance with no treatment-related mortality.
- NOAEL established at 480 mg/kg/day in rats and 300 mg/kg/day in female dogs; 15 mg/kg/day in male dogs due to QTc prolongation risk.
- Pharmacokinetic analysis revealed dose-proportional systemic exposure without JBD0131 accumulation; metabolite DM131 showed moderate accumulation but was identified as a detoxification product.
- Study provides critical foundation for clinical monitoring, highlighting sex-specific sensitivities and metabolite safety.
- JBD0131 demonstrated a favorable preclinical safety profile compared to agents like bedaquiline and pretomanid, supporting development for multidrug-resistant tuberculosis.