Preclinical Concomitant Toxicokinetic Study of Schisandrin B by HPLC–MS/MS

Abstract

Schisandrin B (Sch B), a natural lignan extracted from schisandra chinesis, has exhibited various pharmacological activities including anticancer effects. However, studies on the preclinical toxicokinetic profile of Sch B have not been publicly reported. This study aimed to investigate the preclinical concomitant toxicokinetics of multiple administration of Sch B. Sch B was administered orally to rats and dogs at 150, 300, and 600 mg/kg/day and 50, 100, and 200 mg/kg/day, respectively, for 26 weeks. Plasma concentrations of Sch B were determined by a validated HPLC–MS/MS method. According to the toxicokinetic results, significant gender differences were observed in the rats, and females had higher exposures than males for each dosing group. Toxicokinetic analysis demonstrated a notable accumulation in the plasma of dogs during the repeated administration of Sch B, and the degree of accumulation increased with the increase of the dose. The findings of this study indicated that there were differences in the concomitant toxicokinetics of Sch B between rats and dogs. These results can inform clinical studies and provide valuable insights for future human Sch B risk assessments.