排脓散中桔梗对柚皮苷和芍药苷大鼠体内药动学的影响

In vivo pharmacokinetic study on naringin and paeoniflorin of Painong Powder with or without Platycodonis Radix in rats

目的比较排脓散中桔梗对大鼠体内柚皮苷和芍药苷的药动学影响,研究桔梗的配伍作用。方法 12只健康雄性SD大鼠随机分为排脓散全方组和排脓散缺桔梗方组,按16 g/kg ig给予排脓散全方提取物和排脓散缺桔梗方提取物,于不同时间点眼眶采血,以甘草苷为内标,采用超高效液相-质谱联用技术(UPLC-MS/MS)同时测定大鼠血浆中柚皮苷和芍药苷的浓度。以0.1%甲酸水溶液-甲醇为流动相梯度洗脱,体积流量0.2μL/min,采用电喷雾离子化(ESI)源,负离子方式扫描,多反应检测模式(MRM)检测2种指标成分,采用DAS2.0软件计算药动学参数。结果大鼠ig排脓散全方和排脓散缺桔梗方后,柚皮苷血液药动学参数曲线下面积(AUC0~t)分别为(2 643.22±277.75)、(1 934.01±371.98)μg·h/L,达峰浓度(Cmax)分别为(597.57±22.46)、(477.13±25.67)μg/L,清除率(CL)分别为(821.96±175.64)、(542.21±100.97)L/(h·kg),差异均具有显著性(P<0.05);芍药苷血液药动学参数AUC0~t分别为(3 178.25±235.97)、(1 384.11±320.11)μg·h/L,Cmax分别为(816±28.88)、(402.67±58.22)μg/L,CL分别为(1 102.27±341.17)、(482.59±39.74)L/(h·kg),差异均具有显著性(P<0.05)。结论配伍桔梗后,大鼠血浆中柚皮苷和芍药苷的药动学变化趋势大体相同,表现为达峰时间缩短,吸收程度和达峰浓度增加,清除速率加快,由此验证了桔梗在排脓散中的配伍具有科学合理性,同时为进一步研究排脓散的配伍规律提供参考。

Objective To compare the pharmacokinetic effect of Platycodonis Radix in Painong Powder on naringin and paeoniflorin in rats, and study the compatibility effects of Platycodonis Radix. Methods A total of 12 healthy male SD rats were randomly divided into the Painong Powders full formula group and Painong Powder without Platycodonis Radix group; The solution of Painong Powders full formula and Painong Powder without Platycodi Radix was ig administrated to rats at dose of 16 g/kg. The blood was collected from theretinal vein plexus of rats at predetermined time and pre-prepared with liquiritin as internal standard（IS）. UPLC-MS/MS was adopted to determine the contents of naringin and paeoniflorin. The chromatography was eluted with mobile phase consisted of 0.1% formic acid and methyl alcohol at a flow rate of 0.2 μL/min. ESI sources were adopted to scan in a negative ion scanning mode. Results After ig administration Painong Powder and Painong Powder without Platycodonis Radix, the main pharmacokinetic parameters of naringin were as follow： AUC0-t =（2 643.22 ± 277.75）,（1 934.01 ± 371.98） μg·h/L; Cmax =（597.57 ± 22.46）,（477.13 ± 25.67） μg/L; CL =（821.96 ± 175.64）,（542.21 ± 100.97） L/（h·kg）; Paeoniflorin showed AUC 0-t =（3 178.25 ± 235.97）,（1 384.11 ± 320.11） μg·h/L; Cmax =（816 ± 28.88）,（402.67 ± 58.22） μg/L; CL =（1 102.27 ± 341.17）,（482.59 ± 39.74） L/（h·kg）（P〈0.05）. Conclusion Compared Painong Powders without Platycodonis Radix, the naringin and paeoniflorin in rat plasma showed similar pharmacokinetic changes after oral administration Painong Powders full formula, such as the peak time was shortened, the rate of absorption, peak concentration, and the clearance were accelerated. This study proved scientific compatibility of Platycodonis Radix in Painong Powder and provided a reference for further study of the prescription compatibility regularity in Painong Powders.