caa a22 4500 477128009 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012188625088 doi (NATIONALLICENCE)springer-10.1023/A:1012188625088 Polar Molecular Surface Properties Predict the Intestinal Absorption of Drugs in Humans [Elektronische Daten] [Katrin Palm, Patric Stenberg, Kristina Luthman, Per Artursson1] 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. Plenum Publishing Corporation, 1997 polar molecular surface area nationallicence hydrogen bonding potential nationallicence lipophilicity nationallicence drug absorption nationallicence intestinal drug transport nationallicence membrane permeability nationallicence Palm Katrin Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden aut Stenberg Patric Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden aut Luthman Kristina Department of Organic Pharmaceutical Chemistry, Uppsala University, Box 574, S-, 751 23 Uppsala, Sweden. (e-mail aut Artursson1 Per Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 568-571 0724-8741 14:5<568 1997 14 11095 https://doi.org/10.1023/A:1012188625088 text/html Onlinezugriff via DOI 1 brief-communication jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012188625088 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Palm Katrin Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden aut NATIONALLICENCE 700 1- Stenberg Patric Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden aut NATIONALLICENCE 700 1- Luthman Kristina Department of Organic Pharmaceutical Chemistry, Uppsala University, Box 574, S-, 751 23 Uppsala, Sweden. (e-mail aut NATIONALLICENCE 700 1- Artursson1 Per Department of Pharmaceutics, Uppsala University, Box 580, S, -751 23, Uppsala, Sweden aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 568-571 0724-8741 14:5<568 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer