3种抗人类免疫缺陷病毒一线治疗药物在Caco-2细胞模型中的吸收机制研究  

The mechanism of absorption of three anti-human immunodeficiency virus first-line treatment drugs in Caco-2 cell model

作　　者：高文芳 刘荣[1] GAO Wen-fang;LIU Rong(Department of Pharmacy,Shanghai Public Health Clinical Center,Shanghai 201508,China)

机构地区：[1]上海市公共卫生临床中心药剂科

出　　处：《世界临床药物》2019年第10期693-700,共8页World Clinical Drug

基　　金：上海市公共卫生临床中心院级课题(KY-GW-2019-26)

摘　　要：目的探究3种抗人类免疫缺陷病毒(human immunodeficiency virus,HIV)一线治疗药物拉米夫定、依非韦伦及替诺福韦及其不同组合在Caco-2细胞模型中的吸收机制。方法以Caco-2细胞作为吸收研究的模型,分别测定各种条件下拉米夫定、依非韦伦及替诺福韦的吸收以及在摄取中的相互作用情况。采用高效液相色谱法测定药物的浓度。结果Caco-2细胞分别对拉米夫定、依非韦伦及替诺福韦的Hank's缓冲溶液在30 min内摄取时间近似线性增加,而不同pH条件下细胞摄取量差异无统计学意义(P>0.05)。Caco-2细胞对抗病毒药物的摄取量随浓度的增加呈线性增加。依非韦伦对拉米夫定及替诺福韦在Caco-2细胞中的摄取影响较大。结论在10~200μg/ml浓度范围内,3种药物的摄取量随浓度的增加呈线性增加,说明这3种药物的摄取可能主要是通过被动扩散的方式。在pH 5.0~8.0的介质环境中,药物的摄取无pH依赖性。依非韦伦对于拉米夫定及替诺福韦的细胞摄取产生了较大的竞争作用,导致拉米夫定及替诺福韦其摄取明显减少。Objective To study the absorption mechanism of three anti-human immunodeficiency virus first-line treatment drugs lamivudine,efavirenz,tenofovir and their combination in the Caco-2 cell model.Methods In this paper,the interaction in the absorption and uptake of lamivudine,efavirenz and tenofovir absorption was determined by Caco-2 cells as the model of absorption study.The concentration of drugs was determined by high performance liquid chromatography.Results Caco-2 cells had an approximate linear increase in the uptake time of the HBSS solution of lamivudine,efavirenz and tenofovir respectively in 30 min,and there was no statistical difference in cell intake under different pH conditions(P>0.05).The uptake amount of anti-viral drugs of Caco-2 cells increased linearly with the increase of concentration.The uptake of Caco-2 cells and tenofovir,Caco-2 cells and lamivudine were significantly affected by eferen.Conclusion In the concentration range of 10~200μg/ml,the intake of 3 drugs increased linearly with the increase of concentration linearly,indicating that the uptake of these three drugs may be mainly through passive diffusion.In the medium environment of pH 5.0~8.0,there was no pH dependence of the drug uptaking.The presence of efavirenz greatly competed with cell uptaking of lamivudine and tenofovir,which leading to significant less uptaking of efavirenz.

关 键 词：CACO-2细胞 高效液相色谱法 拉米夫定 依非韦伦 替诺福韦 

分 类 号：R978.7[医药卫生—药品]