大鼠ig牡丹皮提取物后丹皮酚及其代谢产物的药动学研究

Pharmacokinetics of paeonol and its metabolites after oral administration of Moutan Cortex in rats

目的考察ig给予大鼠牡丹皮提取物后,丹皮酚及4种主要代谢产物M1~M4在大鼠体内的药动学特征。方法SD雄性大鼠ig给予不同剂量(0.5、1.0、2.0 g/kg)牡丹皮提取物,于各时间点从大鼠眼底静脉丛取血,收集血浆样品;ig给予1.0 g/kg的牡丹皮提取物,按相应时间段收集大鼠尿液、胆汁和粪便样品。生物样品用乙腈(含0.1%甲酸)沉淀蛋白的方法处理,用建立的超高效液相色谱串联质谱(UPLC-MS/MS)分析方法检测生物样品中丹皮酚及其4种代谢产物质量浓度。结果建立的生物样品分析方法符合分析要求。ig给予大鼠不同剂量(0.5、1.0、2.0 g/kg)牡丹皮提取物后,丹皮酚的tmax分别为(0.15±0.08)、(0.33±0.19)、(0.31±0.13)h;t1/2为(1.16±0.37)、(1.19±0.45)、(1.24±0.35)h;Cmax和AUC0~t随给药剂量的增加而增大,具有剂量依赖性。M1~M4在给药后1 h内也相继达到峰浓度。ig给予1.0 g/kg的牡丹皮提取物后,丹皮酚的代谢产物主要排泄方式为尿液>胆汁>粪便。结论大鼠ig给予牡丹皮提取物后,丹皮酚具有快速吸收、代谢及消除的特点,丹皮酚主要通过尿液途径以代谢产物形式排泄。

Objective To investigate the pharmacokinetics of paeonol and its metabolites M1—M4 in rats after intragastric administration of Moutan Cortex.Methods SD rats were orally administered different doses(0.5,1.0,2.0 g/kg)of Moutan Cortex,and blood was taken from the fundus venous plexus at various time points to collect plasma samples.After given 1.0 g/kg Moutan Cortex extract,urine,bile and feces samples were collected for the corresponding time period.The biological samples were treated with acetonitrile(containing 0.1%formic acid)to precipitate protein,and the established UPLC-MS/MS analysis method was used to detect the content of paeonol and its four metabolites in biological samples.Results The established biological sample analysis method satisfied the analytical requirements.After administered to rats with doses(0.5,1.0,2.0 g/kg)of Moutan Cortex extract,the tmax of paeonol was(0.15±0.08)h,(0.33±0.19)h,(0.31±0.13)h;and t1/2 was(1.16±0.37)h,(1.19±0.45)h,(1.24±0.35)h.Cmax and AUC0-t were increased with the increase of dosage of Moutan Cortex extract,which showed dose-dependent manner.M1—M4 also reached Cmax after 1 h of administration.The main way of excretion of metabolites was confirmed by urine>bile>feces.Conclusion After ig administration of Moutan Cortex,paeonol has the characteristics of rapid absorption,metabolism and elimination and mainly excreted in the form of metabolites through urine.