Oral absorption of cephalosporins is quantitatively predicted from in vitro uptake into intestinal brush border membrane vesicles.
Oral absorption of cephalosporins is quantitatively predicted from in vitro uptake into intestinal brush border membrane vesicles.
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DOI：
10.1016/s0378-5173(01)00664-0
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发表时间：
2001-06
影响因子：
5.8
通讯作者：
R. Kohda-Shimizu;Y. Li;Y. Shitara;K. Ito;Y. Tsuda;H. Yamada;T. Itoh
中科院分区：
文献类型：
--
作者：
R. Kohda-Shimizu;Y. Li;Y. Shitara;K. Ito;Y. Tsuda;H. Yamada;T. Itoh
为建立一种预测经寡肽转运体（PepT1）吸收的药物口服吸收的方法，对头孢菌素类抗生素在大鼠肠刷状边界膜囊（BBMV）中的体外吸收分数(F)进行了预测。利用体外摄取数据，利用Amidon等人提出的完全径向混合（CRM）模型推导出的方程预测人体内头孢菌素的F值(Amidon et al.， J. Pharm；科学69(1980)1369)。在本研究中，在25°C和4°C存在H+梯度的情况下，测量了BBMV的摄取，并计算了摄取间隙（CLuptake）。然后计算由PepT1介导的摄取清除率（ΔCLuptake）为25°C减去4°C时的吸收率。根据本式对ΔCLuptakeand F值进行分析，发现ΔCLuptakeand F之间具有较好的相关性。进一步证明，本方法可以通过几种头孢菌素作为标准，定量预测头孢菌素的F值。
In order to establish a method to predict oral absorption of drugs, which are absorbed by the oligopeptide transporter (PepT1), fraction absorbed (F) of cephalosporin antibiotics was predicted from in vitro uptake into rat intestinal brush border membrane vesicles (BBMV). Using in vitro uptake data, F values of cephalosporins in humans were predicted using the equation derived from the complete radial mixing (CRM) model, which was proposed by Amidon et al. (Amidon et al., J. Pharm. Sci. 69 (1980) 1369). In the present study, uptake into BBMV was measured at 25 and 4°C in the presence of an H+-gradient, and the uptake clearance (CLuptake) was calculated. Clearance for the uptake mediated by PepT1 (ΔCLuptake) was then calculated as CLuptakeat 25°C minus that at 4°C. When ΔCLuptakeand F values were analyzed according to the present equation, fairly good correlation between ΔCLuptakeand F was observed. It was further demonstrated that the present method may be able to quantitatively predict F values of cephalosporins by using several cephalosporins as standards.