Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b(2) on the Pharmacokinetics of Saikosaponin a in Rats

作者：Fu R, Liu J, Xue Y, Zhang Z, Song R · 发表于：European journal of drug metabolism and pharmacokinetics · 年份：2019 · DOI：10.1007/s13318-019-00569-5

BACKGROUND AND OBJECTIVES: Radix Bupleuri (RB, Chaihu in Chinese) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Saikosaponin a (SSa), the most abundant saikosaponin in RB, exhibits various pharmacological activities, including anti-inflammatory, antitumor, antiviral, immunoregulatory, neuromodulatory, and hepatoprotective activities. A comprehensive study of the pharmacokinetic characteristics of SSa is needed to gain a detailed understanding of its pharmacodynamic mechanism. METHODS: Here, we determined the effects of rat strain (Sprague Dawley and Wistar), oral dose, and cotreatment with saikosaponin b2 (SSb2) on the pharmacokinetics of SSa by measuring SSa in plasma via LC-MS/MS. RESULTS: The results showed that the absorption of SSa in Wistar rats was statistically superior to its absorption in Sprague Dawley rats based on pharmacokinetic parameters such as the area under the concentration-time curve (AUC0-t) and the peak concentration (Cmax). Pharmacokinetic studies of different doses of SSa in Wistar rats revealed that the systemic exposure of SSa, based on AUC values, increased disproportionately with dose, indicating that SSa exhibits non-dose-proportional pharmacokinetics. In addition, our studies showed that SSb2, a characteristic component of vinegar-baked Radix Bupleuri (VBRB), inhibits the absorption of SSa in rats. CONCLUSIONS: The pharmacokinetic data for SSa obtained in this study will pl...