Polar Molecular Surface Properties Predict the Intestinal Absorption of Drugs in Humans

Pharmaceutical Research - Tập 14 Số 5 - Trang 568-571 - 1997
Palm, Katrin1, Stenberg, Patric1, Luthman, Kristina2, Artursson1, Per1
1Department of Pharmaceutics, Uppsala University, Uppsala, Sweden
2Department of Organic Pharmaceutical Chemistry, Uppsala University, Sweden. (e-mail

Tóm tắt

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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Pharmaceutical Research

Tập 14 Số 5

568-571

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