Pharmacokinetic Profile and Evaluation of Acute and Subchronic Oral Toxicity of Shikimic Acid in Mice

Shikimic acid, a widely known hydroaromatic compound abundantly found in <i>Illicium verum</i> (commonly known as Chinese star anise), serves as a key intermediate in the synthesis of neuraminidase inhibitors such as oseltamivir. However, its pharmacokinetic (PK) properties and long-term safety profile remain inadequately characterized. This study systematically evaluated its PK behavior following both oral and intravenous administrations, along with its acute toxicity and 28-day subchronic oral toxicity in mice. PK analysis for shikimic acid demonstrated linear and dose-proportional behavior within the intravenous dose range of 4-16 mg/kg. Shikimic acid was rapidly eliminated from plasma, with a short terminal half-life (<i>T</i> _1/2) of 0.76-0.85 h. Despite rapid absorption (<i>T</i> _max, 0.95-1.25 h) following oral administration, a low bioavailability ranging from 11.09 to 20.44% was observed in mice. Acute toxicity testing showed no mortality at oral doses of up to 10,000 mg/kg. In the 28-day subchronic oral toxicity study, mice fed diets containing high (50 g/kg), medium (16.67 g/kg), or low (5.56 g/kg) doses of shikimic acid exhibited no mortality. Hematological assessments revealed slight elevations in neutrophil counts, eosinophil counts, and hematocrit levels in the high-dose group compared to controls. Notably, a significant reduction in triglyceride levels was observed in the high-dose group, suggesting potential hypolipidemic effects for shikimic acid. Collectively, these findings provide foundational data on the PKs, safety, and tolerability of shikimic acid, supporting its further development for potential therapeutic applications.