Pharmaceutical Research

, Volume 14, Issue 5, pp 568–571

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

  • Katrin Palm
  • Patric Stenberg
  • Kristina Luthman
  • Per Artursson1
Article

DOI: 10.1023/A:1012188625088

Cite this article as:
Palm, K., Stenberg, P., Luthman, K. et al. Pharm Res (1997) 14: 568. doi:10.1023/A:1012188625088

Abstract

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.

polar molecular surface area hydrogen bonding potential lipophilicity drug absorption intestinal drug transport membrane permeability 

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Katrin Palm
    • 1
  • Patric Stenberg
    • 1
  • Kristina Luthman
    • 2
  • Per Artursson1
    • 1
  1. 1.Department of PharmaceuticsUppsala UniversityUppsalaSweden
  2. 2.Department of Organic Pharmaceutical ChemistryUppsala UniversitySweden. (e-mail

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