摘要
目的 探讨脾虚证大鼠甘草甜素(Glycyrrhizin,GL)的药物动力学(Pharmacokinetics,PK)特征及其在胃肠机械运动方面的机制。方法 利血平作用于大鼠14 d,制成实验性脾虚证模型,用四君子汤和六味地黄汤反证;用高效液相色谱(HPLC)法测定大鼠体内GL的血药浓度;用高灵敏传感器记录胃和十二指肠运动波。结果 与正常对照组比较(1)脾虚模型组血药—时曲线下面积(AUC),血药最高峰浓度(Cmax);半吸收期(T_(1/2)ka)消除速度常数(β)均减小,转运速度常数(K_(12))增大(P<0.01);(2)脾虚模型组胃、十二指肠运动功能均减弱(P<0.01);(3)经四君子汤预防性治疗的大鼠胃肠运动和GL的PK参数与正常对照组比较差异无显著性意义(P>0.05),但经六味地黄汤治疗组的大鼠各值与正常对照组比较差异有较显著性意义(P<0.05)。结论 脾虚大鼠对经口服GL后的吸收、分布、转运和消除均存在异常;血药浓度和生物利用度降低,GL的有效吸收低;胃肠运动功能减弱,可能是脾虚GL的有效吸收降低的机制之一。
Objective To explore the pharmacokinetic characteristics of gLycyrrhizin in rat model of spleen deficiency syndrome ( RMSDS) and its mechanism in gastrointestinal motility. Methods RMSDS was developed by intramuscular injection of reserpine for 14 days and was confirmed by Si Junzi Tang decoction and Liuwei Di Huang Wan Pills.The blood concentration of glycynhizin in rats was determined by HPLC,and the count and amplitude of movement waves were recorded using sensing element at different parts of stomach and duodenum. Results Compared with normal controls, (1) in RMSDS the area under concentration - time curzve( AUC), maximum coucentration (Cmax), biological half- life (Ti/2 ka) and constant of elimination rate (|3) were decreased but its constant of transfer rate (K12) was increased ( P < 0.01);(2)the mechancal movements of stomach and duodenum were weaker ( P <0.01);(3)there were no sigificant differences in pharmacokinetic parameters in the group administered Si Junzi Tang decoction.Conclusions There are abnormal absorption, transfer and elimination in RMSDS rats;the effective absorption of glycyrrhizin is lower than that in normal rats; blood-drug concentration and bioavailability are declined. The weakening of stomach motility may be one of important mechanisms for pharmacokinetic characteristics of glycyrrhizin in spleen deficiency syndrome.
出处
《武警医学》
CAS
2003年第6期326-328,共3页
Medical Journal of the Chinese People's Armed Police Force
基金
国家自然科学基金(NO39670865
39770886)
