雷公藤固体分散体大鼠在体肠吸收研究  

Intestinal absorption features of Tripterygium wilfordii solid dispersion in rats with single-pass intestinal perfusion model

作　　者：吴珏 刘志宏 林兵 林莉莉 周桂芝 宋洪涛 WU Jue;LIU Zhi-hong;LIN Bing;LIN Li-li;ZHOU Gui-zhi;SONG Hong-tao(900 Hospital of the Joint Logistics Team,Fuzhou 350100,China;College of Pharmacy,Fujian University of Chinese Traditional Medicine,Fuzhou 350108,China)

机构地区：[1]联勤保障部队第九〇〇医院,福建福州350100 [2]福建中医药大学药学院,福建福州350108

出　　处：《中草药》2019年第2期462-470,共9页Chinese Traditional and Herbal Drugs

基　　金：福建省自然科学基金项目(2017J05135);福州总医院院立课题(2016L02)

摘　　要：目的研究雷公藤固体分散体的大鼠肠吸收动力学特征,考察不同肠段、药物浓度、pH值和P-糖蛋白(P-gp)对肠吸收的影响。方法采用大鼠在体单向肠灌流模型,HPLC法测定各指标成分含量,重量法校正数据并计算各指标成分的吸收速率常数(Ka)和表观渗透系数(Papp)。结果将原料药制成固体分散体后,雷公藤各成分在全肠段的Ka较原料药显著增大(P<0.05),雷公藤各指标成分在各肠段均有吸收且存在一定差异。随着药物浓度的升高,各指标成分的吸收均具有饱和现象。酸性环境(pH5.4)有利于各指标成分的吸收,尤其是酸性成分雷公藤红素。加入P-gp抑制剂后,雷公藤红素的吸收与不加P-gp抑制剂比较有显著差异(P<0.05),可能为P-gp底物。结论雷公藤固体分散体各指标成分在全肠段均有吸收,且具有饱和现象;酸性环境有利于各成分的吸收,雷公藤红素吸收过程受药物浓度和P-gp的外排影响,可能为P-gp底物;制成固体分散体能显著提高雷公藤各成分的吸收,提示各指标成分均为生物药剂学系统II类药物,制剂研发过程中增加药物溶解度或可提高制剂的生物利用度。Objective To study the intestinal absorption kinetics of Tripterygium wilfordii(TW) solid dispersions and the effects of different intestinal segments,drug concentrations,pH value,and P-glycoprotein(P-gp) on intestinal absorption.Methods The absorption behavior was investigated in situ with a single-pass intestinal perfusion(SPIP) model in rats.The content of each index component was determined by HPLC.The gravimetric method was used to correct the data and calculate the absorption rate constant(Ka) and apparent permeability coefficient(Papp) of each index component.Results The index components of TW were absorbed in the whole intestine,and the absorption rate constant(Ka) of all the index components of TW solid dispersion was significantly increased than that of extract(P < 0.05),and had some differences among different segments.With the increase of drug concentration,the absorption of each index component had saturation phenomenon,which indicated that it may be carrier-mediated transport mechanism.Acidic environment(pH 5.4) was beneficial to the absorption of various index components,especially the acidic content celastrol.After adding P-gp inhibitor,the Ka and Papp of celastrol were significantly different from those without P-gp inhibitor(P < 0.05),which suggested that it may be the P-gp substrate.Conclusion All the index components of TW solid dispersion are absorbed in the whole intestine and have saturation phenomenon,which suggested the absorption may be carrier-mediated transport mechanism.Acidic environment is beneficial to the absorption of all components.The absorption process of celastrol is affected by drug concentration and P-gp inhibitor,which indicated that it may be P-gp substrate.The preparation of solid dispersing can significantly enhance the absorption of various components of TW,suggesting that all the index components are BCS II drugs,and the bioavailability of the preparation may be improved.

关 键 词：雷公藤 固体分散体 肠吸收动力学 单向肠灌流 雷公藤红素 

分 类 号：R285.5[医药卫生—中药学]