氢氯噻嗪在Caco-2细胞模型中的体外转运研究

采用体外培养的人小肠上皮细胞模型Caco-2考察浓度、时间、P-糖蛋白(P-glyprotein,P-gp)抑制剂维拉帕米(verapamil)以及pH对氢氯噻嗪(hydrochlorothiazide)跨膜转运的影响.氢氯噻嗪双向转运的Papp比值即Papp B→A/Papp A→B均大于1.5.在加入P-gp抑制剂维拉帕米后,氢氯噻嗪PappA→B极显著增大,Papp B→A降低,且Papp B→A/Papp A→B从2.87下降到0.67,加入前后有极显著差异(P0.01),且氢氯噻嗪的吸收转运随pH值的降低而显著增加.结果表明,氢氯噻嗪在Caco-2细胞模型中的吸收可能存在由载体介导的主动转运,同时它还受到P-糖蛋白的外排作用.

Transport characteristics of hydrochlorothiazide in the human intestinal cell line Caco-2

A human intestinal epithelial cell Caco-2 model in vitro cultured had been applied to study the effects of hydrochlorothiazide concentrations,conveying times,P-glyprotein（P-gp） inhibitor verapamil and conveying Liq pHs on the transport of hydrochlorothiazide.In the Caco-2 monolayer model,the apparent permeability coefficients（Papp） of hydrochlorothiazide transport from Basolateral（B） to Apical（A） was larger than that of the opposite direction.In the presence of verapamil,a P-glycoprotein inhibitor,the ratio of Papp B→A and Papp A→B was significantlly decreased from 2.87 to 0.67（P〈0.01）.Meanwhile,the ratio of Papp B→A and Papp A→B in pH 6.0 was significantlly less than that in pH7.4（ratio 0.38 versus 2.81,respectively,P〈0.01）.Results showed that the Absorption of hydrochlorothiazide in Caco-2 cell model should be an active transport mediated by transporter,along with excretion action mediated by P-glycoprotein.