Determination of the passive absorption through the rat intestine using chromatographic indices and molar volume
Determination of the passive absorption through the rat intestine using chromatographic indices and molar volume
复制标题
DOI：
10.1016/s0928-0987(00)00175-5
复制
发表时间：
2001-01-01
影响因子：
4.6
通讯作者：
Legendre, JY
中科院分区：
文献类型：
--
作者：
Genty, M;González, G;Legendre, JY
采用固定化人工膜（IAM）色谱与理化描述符耦合的方法模拟了药物在大鼠肠道内的被动吸收。在IAM PC DD2色谱柱上测定了12种结构不同的化合物的色谱容量因子（log k（IAM）’）。通过大鼠外翻肠囊或非外翻肠囊测定药物对主动转运分子的被动透性（P-a）。通过逐步多元线性回归（MLR）和反向传播神经网络（BPNN）研究了log k(IAM)'、理化描述符与P-a之间的相关性。MLR和BPNN结果表明，log k（IAM）是与P-a相关性最好的描述符。考虑到摩尔体积作为附加描述符，相关性得到了改善。IAM上的保留指数和摩尔体积可以同时用于预测药物的被动吸收。(C) 2001 Elsevier Science B.V.版权所有
Immobilized artificial membrane (IAM) chromatography coupled to physicochemical descriptors was evaluated to model the passive intestinal absorption of drugs through rat gut sacs. The chromatographic capacity factors (log k(IAM)') of 12 structurally diverse compounds were determined on a IAM PC DD2 column. The passive permeabilities (P-a) of the drugs were determined through rat everted gut sacs or through non-everted sacs for actively transported molecules. Correlation studies between log k(IAM)', physicochemical descriptors and P-a were conducted by stepwise multiple linear' regression (MLR) and back-propagation neural network (BPNN). MLR and BPNN showed that log k(IAM)' was the descriptor which correlated best with P-a. Considering the molar volume as an additional descriptor, the correlation was improved. Retention indices on IAM and the molar volume can be used concurrently to predict passive drug absorption. (C) 2001 Elsevier Science B.V. All rights reserved.