Assessment of subchronic toxicity and toxicokinetics of AG NPP709 in Sprague-Dawley rats

Hedera helix L. (HH) leaves and Coptidis rhizoma (CR) have traditionally been used to treat respiratory conditions. AG NPP709, which is formulated using extracts of both these herbs, has been developed as an expectorant and antitussive.The objective was to evaluate the subchronic toxicity and toxicokinetic characteristics of AG NPP709 in laboratory rats.AG NPP709 was orally administered to rats at doses of up to 2.0 g/kg/day for a duration of 13 weeks. Various health parameters were measured throughout the treatment period. At the end of the treatment, a necropsy was conducted and additional parameters were analyzed. Toxicokinetic analyses were also performed on hederacoside C and berberine, the active components of HH leaves and CR, respectively, in the plasma of rats treated with AG NPP709.AG NPP709-treated rats exhibited several health issues, such as reduced feed intake, altered differential white blood cell (WBC) count, increased plasma Alb/Glo ratio in females, and reduced kidney weight in males. However, these changes appeared to be incidental and fell within the typical range for healthy animals of this species. Additionally, toxicokinetic analysis of hederacoside C and berberine showed no accumulation in the plasma of rats during the repeated treatments with AG NPP709.Our study demonstrates that AG NPP709 does not have any harmful effects on rats under experimental conditions. Based upon these findings, the no observed adverse effect level of AG NPP709 can be estimated to be 2.0 g/kg/day in rats.