Prediction of human intestinal absorption of drug compounds from molecular structure.
The absorption of a drug compound through the human intestinal cell lining is an important property for potential drug candidates. Measuring this property, however, can be costly and time-consuming. The use of quantitative structure-property relationships (QSPRs) to estimate percent human intestinal absorption (%HIA) is an attractive alternative to experimental measurements. A data set of 86 drug and drug-like compounds with measured values of %HIA taken from the literature was used to develop and test a QSPR mode. The compounds were encoded with calculated molecular structure descriptors. A nonlinear computational neural network model was developed by using the genetic algorithm with a neural network fitness evaluator. The calculated %HIA (cHIA) model performs wells, with root-mean-square (rms) errors of 9.4%HIA units for the training set, 19.7%HIA units for the cross-validation (CV) set, and 16.0%HIA units for the external prediction set.
Department of Chemistry, Pennsylvania State University, University Park 16802, USA.
M D
MD
Wessel
P C
PC
Jurs
J W
JW
Tolan
S M
SM
Muskal
D006801:Humans; D007408:Intestinal Absorption; D016014:Linear Models; D008954:Models, Biological; D015394:Molecular Structure; D016571:Neural Networks, Computer; D010599:Pharmacokinetics; D013329:Structure-Activity Relationship