Polar molecular surface properties predict the intestinal absorption of drugs in humans

  • Palm K
  • Stenberg P
  • Luthman K
 et al. 
  • 118


    Mendeley users who have this article in their library.
  • 521


    Citations of this article.


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 < or = 60 A2 while drugs that are < 10% absorbed had a PSAd > or = 140 A2. CONCLUSIONS The results indicate that PSAd can be used to differentiate poorly absorbed drugs at an early stage of the drug discovery process.

Author-supplied keywords

  • Drug absorption
  • Hydrogen bonding potential
  • Intestinal drug transport
  • Lipophilicity
  • Membrane permeability
  • Polar molecular surface area

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free