20(R)-人参皂苷Rh2的大鼠肠吸收动力学  

Absorption kinetics of 20(R)-ginsenoside Rh2 in rat intestinal segments

作　　者：顾轶[1,2] 王广基[1] 张经纬[1] 艾华[1] 吕华[1] 谢海棠[3] 贾元威[3] 孙建国[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室 [2]和记黄埔医药(上海)有限公司药物代谢及动力学部,上海201203 [3]皖南医学院弋矶山医院安徽省药物临床评价中心

出　　处：《中国临床药理学与治疗学》2009年第4期368-373,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家"863"计划基金资助项目(2003AA2Z347A);国家自然科学基金资助项目(305722228);江苏省自然科学基金资助项目(BK2005098;BK2006152)

摘　　要：目的:建立准确可靠的测定大鼠血浆中20(R)-人参皂苷Rh2的液相色谱—质谱联用(LC/MS)方法,研究20(R)-Rh2在大鼠不同肠段中的吸收动力学。方法:分离、结扎SD大鼠的不同肠段(十二指肠、空肠、回肠、结肠),制成在体肠袢模型,将20(R)-Rh2按剂量9 mg/kg注入肠袢,于不同时间点眼内眦取血,用LC/MS法测定给药后的血浆中药物浓度,计算吸收动力学参数。结果:本文所建立的大鼠血浆中20(R)-Rh2的LC/MS法线性范围为5～1000 ng/mL(R2=0.9973),日内日间精密度在15%之内,准确度在85%～115%之间。十二指肠、空肠、回肠和结肠肠袢给药后的AUC0-6 h分别为(207±88)、(301±49)、(157±93)和(172±68)ng.mL-1.h,吸收速率常数Ka分别为(3.9±0.4)、(1.6±0.4)、(1.9±0.8)和(1.1±0.9)/h,达峰时间tmax分别为(0.44±0.13)、(1.75±0.50)、(1.13±0.63)和(2.00±1.41)h,达峰浓度分别为(82±17)、(110±11)、(36±8)和(43±7)ng/mL。结论:20(R)-Rh2肠道吸收困难,十二指肠和空肠是它吸收的主要部位。推测膜通透性差和肠道外排转运体是影响Rh2吸收的因素。AIM： To establish a precise and reliable LC/MS assay for determining 20 （R）-Ginsenoside Rh2 in rat plasma and to study the absorption kinetics of 20（R）-Ginsenoside Rh2 in different rat intestinal segments. METHODS： Different rat intestinal segments （duodenum, jejunum, ileum and colon） were isolated and ligated respectively, to form a closed intestinal loop model. 20（R）-Rh2 was injected into the loop directly at a dose of 9 mg/kg. The blood was harvested at different time points after dosage. Concentrations of 20（R）-Ginsenoside Rh2 in plasma were determined by the LC/MS method. The parameters were calculated. RESULTS： 20（R）-Rh2 had a good linearity from 5 to 1000 ng/mL（ R2 = 0.9973） in the LC/MS method established in this paper. The within-day and inter-day precisions were within 15%, and the accuracy was between 85% - 115%. After administering in the intestinal loops, the AUC0-6h were（207 ± 88）,（301 ± 49）, （157 ± 93）and （172± 68） ng·mL^-1·h for duodenum, jejunum, ileum and colon respectively, while the absorption rate constant Ka were （3.9 ± 0.4）,（1.6±0.4）,（1.9±0.8） and（1.1±0.9） /h, respectively. The peak time tmax were（0.44 ± 0.13）, （1.75 ± 0.50）, （1.13 ± 0.63） and （2.00 ± 1.41） respeetively, with the corresponding peak concentrations at （82 ± 17）, （ 110 ± 11 ）, （36 ± 8） and （43 ± 7） ng/mL. CONCLUSION： It is hard for 20（R）-Ph2 to be absorbed in rat intestine. Duodenum and jejunum are its main absorption sites. It is speculated that bad membrane permeability and intestinal efflux transporters are impact factors for its absorption.

关 键 词：20(R)-人参皂苷Rh2 吸收 药代动力学 肠袢 液质联用 

分 类 号：R965.2[医药卫生—药理学]