目的 研究白芍总苷中4个活性成分（芍药苷、芍药内酯苷、没食子酰芍药苷和苯甲酰芍药苷）在正常和四氯化碳（carbon tetrachloride，CCl₄）诱导急性肝损伤大鼠体内的药动学过程，并比较其差异。方法 参照临床给药剂量给SD大鼠ig白芍总苷后，采集不同时间点大鼠血清，建立LC-MS方法测定血药浓度，采用WinNonlin5.3药动学软件计算各成分药动学参数，并进行统计学分析。结果 没食子酰芍药苷和苯甲酰芍药苷的入血浓度较低，可能大部分迅速代谢为中间产物芍药苷。肝损伤使主要成分芍药苷、芍药内酯苷在大鼠体内的半衰期（t_1/2）和平均滞留时间（MRT）显著延长（P＜0.05、0.01），药时曲线下面积（AUC）显著增加（P＜0.05、0.01），清除率（CL/F）显著降低（P＜0.05、0.01）；没食子酰芍药苷在2组大鼠体内的药动学参数无显著性差异，但其在肝损伤大鼠体内的药-时曲线出现双峰现象；苯甲酰芍药苷在2组大鼠体内的t_1/2和MRT_0~∞无显著变化，但肝损伤使其AUC显著增加（P＜0.01）。结论 为进一步探究白芍总苷多成分协同的保肝作用机制提供实验基础，同时为该中药的临床合理用药提供指导参考。

Objective To study the pharmacokinetics of four active ingredients (paeoniflorin, albiflorin, galloylpaeoniflorin and benzoylpaeoniflorin) of total glucosides of paeony (TGP) in normal and carbon tetrachloride (CCl₄)-induced acute hepatic injury rats, and then compare their differences in pharmacokinetic parameters. Methods TGP was intragastrically administered to SD rats with the reference of its clinical dosage. After administration, serum of rats was collected in planed interval time points. LC-MS method was established to determine drug concentrations in serum. The pharmacokinetic parameters were calculated using WinNonlin 5.3 pharmacokinetic software, and their difference in normal and hepatic injury rats were statistically analyzed. Results The concentration of galloylpaeoniflorin and benzoylpaeoniflorin were relatively lower than paeoniflorin in blood because they might mainly be metabolized to the intermediate compound paeoniflorin. For the main ingredients of paeoniflorin and albiflorin, their half-life (t_1/2) and mean residence times (MRT) were significantly extended (P < 0.05, 0.01), area under drug-time curve (AUC) were significantly increased (P< 0.05, 0.01), and clearance (CL/F) were significantly reduced in hepatic injury rats when comparing with normal rats (P < 0.05, 0.01). For galloylpaeoniflorin, there were no significant differences of pharmacokinetic parameters in two groups of rats, but it presented double peak of drug-time curve in hepatic injury rats. For benzoylpaeoniflorin, there were no significant differences of t_1/2and MRT_0～∞ in two groups of rats, but its AUCs were significantly increased in hepatic injury rats than in normal rats (P < 0.01). Conclusion This study would provide an experimental basis for further exploring the liver protective mechanism of the synergistic effect of TGP and provide guidance and reference for its clinical rational use.

R285.61

国家自然科学基金资助项目（81503338）；浙江省基础公益研究计划项目（LGF22H280004，LGD22H160004）；嘉兴市科技计划项目（2020AY10022）；嘉兴学院重点SRT资助项目（8517221147）