Pharmacokinetics and Toxicity Study of a Single Intravenous Dose of Distilled Extract of Zanthoxylum piperitum in ICR Mice

Abstract Background This study aimed to investigate the pharmacokinetics and acute toxicity of a single intravenous dose of a distilled extract of Zanthoxylum piperitum (deZP) in ICR mice. The focus was on understanding the absorption, distribution, and elimination of terpinen-4-ol, the major active component, as well as assessing the safety of the administered dose. Methods ICR mice were administered a single intravenous dose of deZP (2.4 mg/kg). Plasma concentrations of terpinen-4-ol were measured at various time points using LC–MS/MS to calculate pharmacokinetic parameters (Cmax , Tmax_obs , half-life, and clearance rate). Acute toxicity was evaluated by monitoring clinical signs, mortality, and biochemical markers. Results Terpinen-4-ol was rapidly absorbed, reaching a peak plasma concentration (Cmax ) of 609.0 ng/mL within 0.083 h (Tmax_obs). It exhibited a short half-life of 0.168 h and a high clearance rate of 194.1 mL/min/kg. No mortality or significant clinical signs of toxicity were observed. Biochemical parameters, including liver and kidney function markers, remained within normal ranges, indicating the dose was well-tolerated. Conclusions The pharmacokinetic profile of deZP in ICR mice is characterized by the rapid absorption and elimination of terpinen-4-ol. The toxicity assessment indicates good tolerability at the tested dose, suggesting a strong safety profile. These findings provide a foundation for further exploration of deZP’s therapeutic potential. Graphical Abstract The distilled extract containing terpinen-4-ol as a major component was administered intravenously at a single dose of 2.4 mg/kg. Pharmacokinetic analysis revealed rapid systemic elimination with a short half-life (t₁/₂ = 0.168 h), a Tmax of 0.083 h, and a Cmax of 609.0 ng/mL. Safety evaluation, including liver and kidney biochemical markers (AST, ALT, BUN, creatinine, bilirubin, ALP, albumin, TC/HDL-C/TG), showed no significant abnormalities, and no acute toxicity was observed. These findings indicate that deZP is rapidly cleared from circulation and is well-tolerated in mice at the tested dose.