Pade V, Stavchansky S
Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin, 78712, USA.
J Pharm Sci. 1998 Dec;87(12):1604-7. doi: 10.1021/js980111k.
The objective of this investigation was to establish a relationship between drug permeability and solubility in vitro and the extent of drug absorption in humans. We selected drugs with varying permeabilities and solubilities with the aim of establishing a relationship between permeability and solubility measurements in vitro and the extent of absorption in vivo. Effective permeability coefficients of the model drugs (naproxen, phenytoin, propranolol, diltiazem, salicylic acid, ephedrine, cimetidine, chlorothiazide, and furosemide) at 37 degrees C and pH 7.2 were estimated using the Caco-2 cell line. Saturation solubilities of the model drugs were estimated at pH 7.2 and at 37 degrees C. Data obtained from the permeability and solubility experiments were employed in classifying the drugs into high and low permeability-solubility groups. The permeability coefficients ranged from 1x10(-7) to 4x10(-5) cm/s, and a good correlation was observed between the permeability coefficients in Caco-2 cells and percent absorbed in humans. Drugs in the high permeability, high solubility class are completely absorbed (90% or higher). The study results indicate that there is a strong link between permeability measured in Caco-2 cells, solubility, and fraction of drug absorbed in humans.
本研究的目的是建立药物体外渗透性和溶解性与人体药物吸收程度之间的关系。我们选择了具有不同渗透性和溶解性的药物，旨在建立体外渗透性和溶解性测量值与体内吸收程度之间的关系。使用Caco-2细胞系估算了模型药物（萘普生、苯妥英、普萘洛尔、地尔硫卓、水杨酸、麻黄碱、西咪替丁、氯噻嗪和呋塞米）在37℃和pH 7.2条件下的有效渗透系数。在pH 7.2和37℃条件下估算了模型药物的饱和溶解度。将渗透性和溶解性实验获得的数据用于将药物分为高渗透性-高溶解性组和低渗透性-低溶解性组。渗透系数范围为1×10⁻⁷至4×10⁻⁵cm/s，并且在Caco-2细胞中的渗透系数与人体吸收百分比之间观察到良好的相关性。高渗透性、高溶解性类别的药物被完全吸收（90%或更高）。研究结果表明，在Caco-2细胞中测得的渗透性、溶解性与人体吸收的药物分数之间存在紧密联系。
