Predicting Drug Absorption: How Nature Made It a Difficult Problem

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 303; no. 3; pp. 889 - 895
• Main Authors: Burton, Philip S, Goodwin, Jay T, Vidmar, Thomas J, Amore, Benny M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.12.2002
• Subjects: Administration, Oral; Animals; Dose-Response Relationship, Drug; Forecasting; Humans; Intestinal Absorption - physiology; Permeability; Pharmaceutical Preparations - metabolism; Structure-Activity Relationship
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.102.035006

Significant recent work has focused on predicting drug absorption from structure. Several misperceptions regarding the nature of absorption seem to be common. Among these is that intestinal absorption, permeability, fraction absorbed, and, in some cases, even bioavailability, are equivalent properties and can be used interchangeably. A second common misperception is that absorption, permeability, etc. are discrete, fundamental properties of the molecule and can be predicted solely from some structural representation of the drug. In reality, drug absorption is a complex process dependent upon drug properties such as solubility and permeability, formulation factors, and physiological variables, including regional permeability differences, pH, lumenal and mucosal enzymology, and intestinal motility, among others. This article will explore the influence of these different variables on drug absorption and the implications with regards to attempting to develop predictive drug absorption algorithms.