栀子柏皮汤不同配伍在大鼠体内的药代动力学研究

Pharmacokinetic Study on Different Compatibilities of Zhizi Bopi Decoction in Rats

摘要:

目的：通过测定栀子苷单体及栀子（ZZ）、栀子-黄柏（ZZ-HB）、栀子-甘草（ZZ-GC）和栀子柏皮汤（ZZBPD）4种汤剂中栀子苷在大鼠体内的药动学参数，考察栀子柏皮汤配伍的变化对栀子苷药动学的影响。方法：将SD大鼠随机分为5组，分别灌胃给予含等量栀子苷的栀子苷单体溶液、栀子、栀子-黄柏、栀子-甘草和栀子柏皮汤，采用HPLC测定给药后0.08，0.25，0.5，0.75，1，1.5，2，4，6，8，10 h时的血药浓度，采用3P97软件计算药动学参数。结果：栀子苷单体及4种汤剂中栀子苷在大鼠体内的药动学参数有明显差别（P<0.05），与栀子苷单体组相比，4组汤剂的AUC及T_1/2均显著增加，其中栀子柏皮汤的C_max，T_max，T_1/2，AUC_0-t，AUC_0-∞均高于其他各配伍组，栀子-黄柏、栀子-甘草和栀子柏皮汤组的AUC_0-t，AUC_0-∞及T_1/2均高于栀子组，栀子-甘草和栀子柏皮汤组T_max明显延长。结论：栀子柏皮汤不同配伍对栀子苷的药动学存在不同的影响，汤剂给药的生物利用度高于单体给药，全方组给药的生物利用度要显著高于其他各配伍组，说明药材之间的相互作用能促进栀子苷的吸收，延缓其消除，进而提高其生物利用度。

Abstract:

Objective: To obtain pharmacokinetics parameters of geniposide in pure geniposide, Gardeniae Fructus(ZZ), ZZ-Phellodendri Chinensis Cortex(HB), ZZ-Glycyrrhizae Radix et Rhizoma(GC) and Zhili Bopi decoction(ZZBPD) and to investigate the effect of the different recipes of ZZBPD on the pharmacokinetics of geniposide. Method: Thirty rats were randomly divided into five groups, and were administered pure geniposide, ZZ, ZZ-HB, ZZ-GC and ZZBPD, respectively. The plasma concentration of four recipes at 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10 h were determined by HPLC, and the pharmacokinetics parameters of geniposide in these recipes were consequently computed by software program 3P97. Result: The differences of the predominant parameters of geniposide in rat plasma of the five groups were considered to be noticeable (P<0.05). Compared to administration of geniposide alone, the pharmacokinetic parameters (AUC_0-t, AUC_0-∞, T_1/2) were remarkably enhanced following oral administration of ZZ, ZZ-HB, ZZ-GC, ZZBPD. The C_max, T_1/2, AUC_0-t and AUC_0-∞ of ZZBPD were remarkably enhanced compared to other four groups. The AUC_0-t, AUC_0-∞, T_1/2 of ZZ-HB, ZZ-GC and ZZBPD were higher than ZZ. The T_max of ZZ-GC and ZZBPD were longer than ZZ and ZZ-HB. Conclusion: Different recipes of ZZBPD had different impact on the pharmacokinetics of geniposide. The bioavailability of geniposide in decoctions were higher than in monomer and the bioavailability of geniposide in ZZBPD was higher than other groups. It can be deduced that herb-herb interaction may increase the absorption, delay the elimination, and significantly improve the oral bioavailability of geniposide in rats.