Pharmacokinetic and Safety Evaluation of MBZM-N-IBT, A Lead Against Chikungunya Virus

Abstract

Chikungunya virus (CHIKV) infection was previously found to be inhibited by MBZM-N-IBT both in vitro and in vivo. To further assess its suitability for in vivo application, toxicity and pharmacokinetics were investigated. It showed no acute toxicity orally with an estimated LD50 of more than 5000 mg/kg in rats. While it showed toxicity at 1000 mg/kg in the chronic toxicity study, it was better tolerated at 500 mg/kg by rats. At 50 mg/kg, it was found to be safe in a 9-month study. A pharmacokinetic study revealed Tmax less than the gastric emptying time. High plasma protein binding supported its higher elimination half-life. In silico analysis predicted 22 metabolites. The majority of these metabolites fall in OECD class 5 and support the low toxicity of MBZM-N-IBT.