ADME evaluation: 2. A computer model for the prediction of intestinal absorption in humans

Purpose: To develop a computational method to rapidly evaluate human intestinal absorption, one of the drug properties included in the term ADME ( Absorption, Distribution, Metabolism, Excretion). Poor ADME properties are the most important reason for drug failure in clinical development. Methods: The model developed is based on a modified contribution group method in which the basic parameters are structural descriptors identified by the case program, together with the number of hydrogen bond donors. Results: The human intestinal absorption model is a quantitative structure–activity relationship (QSAR) that includes 37 structural descriptors derived from the chemical structures of a data set containing 417 drugs. The model was able to predict the percentage of drug absorbed from the gastrointestinal tract with an r 2 of 0.79 and a standard deviation of 12.32% of the compounds from the training set. The standard deviation for an external test set (50 drugs) was 12.34%. Conclusions: The availability of reliable and fast models like the one we propose here to predict ADME/Tox properties could help speed up the process of finding compounds with improved properties, ultimately making the entire drug discovery process shorter and more cost efficient.