Polar Molecular Surface Properties Predict the Intestinal Absorption of Drugs in Humans
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Purpose. A theoretical method has been devised for prediction of drug absorption after oral administration to humans.
Methods. Twenty structurally diverse model drugs, ranging from 0.3 to 100% absorbed, were investigated. The compounds also displayed diversity in physicochemical properties such as lipophilicity, hydrogen bonding potential and molecular size. The dynamic molecular surface properties of the compounds were calculated, taking into account their three-dimensional shape and flexibility.
Results. An excellent sigmoidal relationship was established between the absorbed fraction after oral administration to humans (FA) and the dynamic polar molecular surface area (PSAd) (r2 = 0.94). The relationship was stronger than those obtained for more established predictors of drug absorption. Drugs that are completely absorbed (FA > 90%) had a PSAd ≤ 60 Å2 while drugs that are < 10% absorbed had a PSAd > 140 Å2.
Conclusions. The results indicate that PS Ad can be used to differentiate poorly absorbed drugs at an early stage of the drug discovery process.
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- Polar Molecular Surface Properties Predict the Intestinal Absorption of Drugs in Humans
Volume 14, Issue 5 , pp 568-571
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- polar molecular surface area
- hydrogen bonding potential
- drug absorption
- intestinal drug transport
- membrane permeability
- Industry Sectors
- Author Affiliations
- 1. Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden
- 2. Department of Organic Pharmaceutical Chemistry, Uppsala University, Box 574, S-, 751 23 Uppsala, Sweden. (e-mail