脉君安片中主要成分对氢氯噻嗪在Caco-2细胞模型中转运的影响

利用人源结肠腺癌细胞系Caco-2细胞单层模型, 研究了脉君安片中主要降压活性成分葛根素、钩藤碱与氢氯噻嗪配伍使用前后对氢氯噻嗪体外吸收与转运的影响, 探讨了氢氯噻嗪与葛根素、钩藤碱配伍使用时在吸收阶段的药物相互作用。结果表明, 氢氯噻嗪在Caco-2单层细胞模型中的吸收可能存在由载体介导的主动转运, 葛根素能减少P-糖蛋白 (P-gp), 对氢氯噻嗪的外排, 钩藤碱对氢氯噻嗪的吸收转运无显著影响, 葛根素、钩藤碱与氢氯噻嗪合用能增强氢氯噻嗪的吸收。同时, 实验还发现氢氯噻嗪可能是P-gp的作用底物, 且pH值对氢氯噻嗪的转运有重要影响, 在弱酸性条件下, 氢氯噻嗪的吸收比在中性条件下好。

Effect of major components of Maijunan tablets on the transport of hydrochlorothiazide in Caco-2 cell monolayer model

To study the effects of major components of Maijunan tablets, puerarin (Pue) and rhynchophylline (Rhy) on the transport of hydrochlorothiazide (Hct) Caco-2 cell monolayer model, the transport parameters of Hct, such as apparent permeability coefficient (P_{app (B→A)} and P_{app (A→B)}) and the ratio of P_{app (B→A)} versus P_{app (A→B)}, were studied and compared when Hct was used solely and co-used with Pue and/or Rhy.  The effects of drug concentrations, conveying times, P-glyprotein (P-gp) inhibitor verapamil and conveying Liq pH values on the transport of Hct in the above conditions were also investigated.  The results indicated that the absorption of Hct in Caco-2 cell monolayer model could be a carrier-mediated active transport, along with the excretion action  mediated by P-gp.  Pue can decrease the excretion action of Hct mediated by P-gp, and Rhy had no significant effect on the transport of Hct.  The co-use of Hct, Pue and Rhy enhanced the absorption of Hct.  Meanwhile, conveying Liq pH value had significant influence on the transport of Hct.  The absorption of Hct at pH 6.0 was higher than that at pH 7.4.