20(R)-人参皂苷Rh2的大鼠肠吸收动力学

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (4): 368-373.

20(R)-人参皂苷Rh2的大鼠肠吸收动力学

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

¹中国药科大学药物代谢动力学重点实验室, 南京210009, 江苏;
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, 芜湖241001, 安徽

收稿日期:2008-12-06 修回日期:2009-03-01 发布日期:2020-10-29
通讯作者: 王广基,男,博士,教授,博士生导师,研究方向:药代动力学。Tel:025-83271128 E-mail:guangjiwang@hotmail.com
作者简介:顾轶,男,博士,工程师,研究方向:药代动力学。Tel:021-50790088 E-mail:gooey@vip.sina.com
基金资助:
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)

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

GU Yi^1,2, WANG Guang-ji¹, ZHANG Jing-wei¹, AI Hua¹, LV Hua¹, XIE Hai-tang³, JIA Yuanwei³, SUN Jian-guo¹

¹Key Laborary of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009,Jiangsu, China;
²DMPK and Tox Group, Hutchison MediPharma Ltd ., Shanghai 201203, China;
³Anhui Provincial Center for Drug Clinical Evaluation, Wannan Medical College Affiliated Yijishan Hospital, Wuhu 241001,Anhui, China

Received:2008-12-06 Revised:2009-03-01 Published:2020-10-29

摘要/Abstract

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9mgkg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5～1000ng/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AUC0-6h分别为(207±88)、(301±49)、(157±93)和(172±68)ng·mL-1·h,吸收速率常数K_a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。

关键词: 20(R)-人参皂苷Rh2, 吸收, 药代动力学, 肠袢, 液质联用

Abstract: 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 AUC0-6 h 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 t max were(0.44±0.13),(1.75±0.50), (1.13±0.63)and (2.00±1.41) respectively , with the corresponding peak concentrations at (82±17), (110±11), (36±8)and (43±7)ng/mL.CONCLUSION: It is hard for 20(R)-Rh2 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.

Key words: 20 (R)-Ginsenoside Rh2, absorption, pharmacokinetics, intestinal loop, LC/MS

中图分类号:

R965.2

顾轶, 王广基, 张经纬, 艾华, 吕华, 谢海棠, 贾元威, 孙建国. 20(R)-人参皂苷Rh2的大鼠肠吸收动力学[J]. 中国临床药理学与治疗学, 2009, 14(4): 368-373.

GU Yi, WANG Guang-ji, ZHANG Jing-wei, AI Hua, LV Hua, XIE Hai-tang, JIA Yuanwei, SUN Jian-guo. Absorption kinetics of 20(R)-ginsenoside Rh2 in rat intestinal segments[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(4): 368-373.

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