Biopharmaceutics classification of selected β-blockers:: Solubility and permeability class membership
Biopharmaceutics classification of selected β-blockers:: Solubility and permeability class membership
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DOI：
10.1021/mp070028i
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发表时间：
2007-07-01
影响因子：
4.9
通讯作者：
Yu, Lawrence X.
中科院分区：
文献类型：
--
作者：
Yang, Yongsheng;Faustino, Patrick J.;Yu, Lawrence X.
本研究的目的是测定7种β受体阻滞剂（醋丁洛尔、阿替洛尔、拉贝洛尔、美托洛尔、纳多洛尔、索他洛尔和噻吗洛尔）的渗透性和溶解度，并根据生物药剂学分类系统（BCS）对其进行分类。使用Caco-2细胞系测量表观渗透系数（P-app），并在37 ℃下在1.0-7.5的pH范围内测定溶解度。渗透系数范围为1.0 × 10（-7）~ 4.8 × 10（-5）CM/S。根据研究中观察到的体外渗透性和溶解度数据，拉贝洛尔、美托洛尔和噻吗洛尔可归类为BCS I类药物，而醋丁洛尔、阿替洛尔和纳多洛尔属于BCS III类药物。除索他洛尔外，所有药物在Caco-2细胞中的渗透系数与报告的人体肠道吸收程度一致。索他洛尔在Caco-2细胞系中表现出低渗透性，但人体肠道吸收程度超过90%。通过Caco-2单层的低渗透性可能在很大程度上与其低亲脂性有关。此外，体内和体外细胞间连接紧密性的差异可能部分导致体内和体外索他洛尔渗透性的差异。
The purpose of this study was to determine the permeability and solubility of seven beta-blockers (acebutolol, atenolol, labetalol, metoprolol, nadolol, sotalol, and timolol) and to classify them according to the Biopharmaceutics Classification System (BCS). Apparent permeability coefficients (P-app) were measured using the Caco-2 cell line, and the solubility was determined at 37 degrees C over a pH range of 1.0-7.5. The permeability coefficients ranged from 1.0 x 10(-7) to 4.8 x 10(-5) CM/S. On the basis of the in vitro permeability and solubility data observed in the study, labetolol, metoprolol, and timolol can be categorized as BCS Class I drugs, whereas acebutolol, atenolol, and nadolol belong to BCS Class III. The permeability coefficients in Caco-2 cells were consistent with the reported extent of intestinal absorption in humans for all drugs except sotalol. Sotalol displayed low permeability in the Caco-2 cell line, but the extent of intestinal absorption in humans is over 90%. The low permeability through the Caco-2 monolayers might be largely related to its low lipophilicity. In addition, the difference between the tightness of the intercellular junction in vivo and in vitro may partially contribute to this disparity in the sotalol permeability of in vivo and in vitro.