Predicting the impact of physiological and biochemical processes on oral drug bioavailability
Predicting the impact of physiological and biochemical processes on oral drug bioavailability
复制标题
DOI：
10.1016/s0169-409x(01)00179-x
复制
发表时间：
2001-10-01
影响因子：
16.1
通讯作者：
Bolger, MB
中科院分区：
文献类型：
--
作者：
Agoram, B;Woltosz, WS;Bolger, MB
本文综述了近年来应用于药物传递和生物药剂学领域的计算方法的进展，重点介绍了生理和生化因素对模拟胃肠道吸收和生物利用度的影响的预测。我们的应用胃肠道模拟口服药物的吸收和生物利用度的预测将被描述。首先，我们收集了文献数据，或者我们通过将统计方法应用于一组2D和3D分子描述符来估计生物制药特性。其次，我们整合了高级房室吸收和转运（ACAT）模型的微分方程，以确定药物释放（控释）、溶出、被动和载体介导吸收以及饱和代谢和外排的速率、程度和大致胃肠道位置。我们预测吸收分数，生物利用度和CP与时间曲线的常见药物，并比较这些估计文献数据。我们说明了模拟的生理和生化过程对口服药物生物利用度的影响。(C)2001年，爱思唯尔科学。All rights reserved.
Recent advances in computational methods applied to the fields of drug delivery and biopharmaceutics will be reviewed with a focus on prediction of the impact of physiological and biochemical factors on simulation of gastrointestinal absorption and bioavailability. Our application of a gastrointestinal simulation for the prediction of oral drug absorption and bioavailability will be described. First, we collected literature data or we estimated biopharmaceutical properties by application of statistical methods to a set of 2D and 3D molecular descriptors. Second, we integrated the differential equations for an advanced compartmental absorption and transit (ACAT) model in order to determine the rate, extent, and approximate gastrointestinal location of drug liberation (for controlled release), dissolution, passive and carrier-mediated absorption, and saturable metabolism and efflux. We predict fraction absorbed, bioavailability, and CP vs. time profiles for common drugs and compare those estimates to literature data. We illustrate the simulated impact of physiological and biochemical processes on oral drug bioavailability. (C) 2001 Elsevier Science BY. All rights reserved.