Breitkreutz J
Institute for Pharmaceutical Technology, Westphalien Wilhelms University, Münster, Germany.
Pharm Res. 1998 Sep;15(9):1370-5. doi: 10.1023/a:1011941319327.
The purpose of this study was to investigate the use of solubility parameters for the prediction of gastrointestinal absorption sites and absorption durations of drugs.
Three-dimensional solubility parameters of drug substances were calculated using an advanced parameter set based on the group contribution methods of Fedors and Van Krevelen/Hoftyzer. The results of the calculations were illustrated via Bagley diagram and related to absorption data reported in the literature.
Solubility parameters of drugs which are known to be absorbed over a long period in human's digestive tract were found in a limited area within the Bagley diagram. From the three-dimensional solubility parameters of these substances, a region for optimal absorption with the centre coordinates delta(v)=20.3 (J x cm(-3))(0.5) and delta(h)=11.3 (J x cm(-3))(0.5) could be derived. Drugs with absorption sites along the whole gastrointestinal tract were found in this area. Drugs which are preferably absorbed from upper parts of the intestine are located in another typical region with partial solubility parameters delta(h) of more than 17 (J x cm(-3))(0.5).
The method which is presented in this paper appears as a simple but effective method to estimate the absorption behaviour of new substances in drug research and development.
本研究旨在探讨利用溶解度参数预测药物的胃肠道吸收部位及吸收持续时间。
采用基于费多斯（Fedors）以及范克雷维伦/霍夫蒂泽（Van Krevelen/Hoftyzer）基团贡献法的先进参数集计算药物物质的三维溶解度参数。计算结果通过巴格利图（Bagley diagram）进行说明，并与文献报道的吸收数据相关联。
在巴格利图的一个有限区域内发现了已知在人体消化道中长时间吸收的药物的溶解度参数。从这些物质的三维溶解度参数中，可以得出一个最佳吸收区域，其中心坐标为δ(v)=20.3（J·cm⁻³）⁰.⁵ 且δ(h)=11.3（J·cm⁻³）⁰.⁵ 。在该区域发现了沿整个胃肠道有吸收部位的药物。优选从肠道上部吸收的药物位于另一个典型区域，其部分溶解度参数δ(h)大于17（J·cm⁻³）⁰.⁵ 。
本文提出的方法似乎是一种在药物研发中估计新物质吸收行为的简单而有效的方法。
