药物体外转运模型及普萘洛尔异构体转运动力学研究

Enantioselective transport of R/S-propranolol in Caco-2 cell monolaysers

目的:用近年来最具代表性的研究口服药物吸收机制的Caco-2细胞单层模型,研究盐酸普萘洛尔异构体的吸收及其吸收机制。方法:建立Caco-2细胞单层模型,研究不同浓度不同时间点该药物异构体的转运情况,通过柱前衍生化的RP—HPLC法检测盐酸普萘洛尔的异构体。结果:盐酸普萘洛尔吸收完全,主要为被动吸收,其异构体在Caco-2细胞模型上吸收无手性选择性。结论:本文建立了Caco-2细胞模型,并进行了完整性评价,表明Caco-2细胞模型完整性良好,将其用于手性药物盐酸普萘洛尔的吸收转运实验。同时还建立了柱前衍生化的RP-HPLC法,可以在20min内分离测定盐酸普萘洛尔异构体,方法操作简便、精密度好、结果准确可靠。

Objective：to study the absorption and absorption characteristics of isomer of propranolol hydrochloride in Caco-2cell monolayers model,which have taken as the most representative model to investigate the absorption mechanism of oral drug in recent years. Methods：Caco-2 cell monolayers model was set up to study transport of isomer of propranolol hydrochloride. RP-HPLC method was applied to analyze isomer of propranolol hydrochloride through precolumn derivatization. Results：Propranolol hydrochloride was absorbed completely,and was a passive diffusion mechanism. There was no chiral selectivity of transport and absorption of them across Caco-2 cell monolayers. Condusion：Caco-2 cell model was established and the cell integrity was evaluated. The integrity of Caco-2 cell was in good condition,which could be used to study the absorption and transport. RP-HPLC method was established to separated isomer of propranolol hydrochloride within 20 min by precolumn derivatization. The method is convenient, sensitive,accurate and suitable for the analysis of telbivudine.