脉君安片中主要成分对氢氯噻嗪在Caco-2细胞模型中转运-药学学报.PDF

104 药学学报 Acta Pharmaceutica Sinica 2010, 45 ( 1) : 104 108 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 廖晓欢, 王俊俊, 高明勇, 高 倩, 陈 勇* (湖北大学中药生物技术省重点实验室, 湖北 武汉 430062) 摘要: 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 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。 关键词: 氢氯噻嗪; 葛根素; 钩藤碱; Caco-2 单层细胞模型; 转运; P-糖蛋白 中图分类号: R964 文献标识码:A 文章编号: 05 13-4870 (2010) 01-0104-05 Effect of major components of Maijunan tablets on the transport of hydrochlorothiazide in Caco-2 cell monolayer model * LIAO Xiao-huan, WANG Jun-jun, GAO Ming-yong, GAO Qian, CHEN Yong (Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei University, Wuhan 430062, China) Abstract: To study the effects of maj or 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 (Papp (B A) and Papp (A B)) and the ratio of Papp (B A) versus Papp (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 tra