体外外翻肠囊法评价不同药物的渗透性  

Evaluation permeability of different drug by in vitro everted gut sac model

作　　者：吴蕊男 唐敏[1] 邢力允 何爽 王红平 刘峰 袁军 黄园[1] WU Ruinan;TANG Min;XING Liyun;HE Shuang;WANG Hongping;LIU Feng;YUAN Jun;HUANG Yuan(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;Sichuan Institute of Food and Drug Control,Chengdu,Sichuan,611731 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041 [2]四川省食品药品检验检测院,四川成都611731

出　　处：《华西药学杂志》2021年第1期15-18,共4页West China Journal of Pharmaceutical Sciences

基　　金：四川省科学技术厅项目(编号:2018SZ0001)。

摘　　要：目的建立体外外翻肠囊模型并用于不同渗透性药物的初步评价。方法利用乳酸脱氢酶法考察体外外翻肠囊模型中肠段在体外环境中的活性。将一定浓度的卡马西平、茶碱、特布他林、依那普利和荧光黄溶液加至外翻肠囊模型的肠囊黏膜侧,吸取不同肠段、不同时间的浆膜侧溶液,用液质联用法测定药物跨膜进入浆膜侧的浓度,并计算表观渗透系数(Papp)。结果体外外翻肠囊模型在90 min内能较好地保持肠段的体外活性。生物药剂学分类系统中高渗透性的卡马西平和茶碱、中渗透性的特布他林、低渗透性的依那普利的Papp与渗透性高低具有相关性,渗透性高,Papp更大。结论初步构建了体外评价药物渗透性的模型,可以对不同药物的渗透性进行区分和划定。OBJECTIVE To establish an in vitro everted gut sac model,and to evaluate drug permeability by this model.METHODS Firstly,the viability of in vitro gut sac was investigated by lactic dehydrogenase( LDH) assay. Carbamazepine,theophylline,terbutaline,enalapril or fluorescein was added to mucosal side of everted gut sac,and samples were taken from serosal side at determined time. Concentration of drug across the intestinal epithelium was determined by liquid chromatography-mass spectrometry. Finally,apparent permeability coefficient( Papp) was calculated to evaluate the permeability of drugs.RESULTS LDH assay showed good viability of in vitro gut sac for 90 min. The Papp value of different drugs in this model are relevant to BCS classification for permeability. CONCLUSION The in vitro everted gut sac model established in this research is robust to differentiate and rank different drug with permeability.

关 键 词：外翻肠囊法 体外评价 生物药剂学分类系统 表观渗透系数 渗透性 生物等效性试验豁免 乳酸脱氢酶 高效液相色谱-质谱联用 

分 类 号：R94[医药卫生—药剂学]