Structure-ADME relationship: still a long way to go?
BACKGROUND
Theoretical models for predicting absorption, distribution, metabolism and excretion (ADME) properties play increasingly important roles in support of the drug development process.


OBJECTIVE
We briefly review the in silico prediction models for three important ADME properties, namely, aqueous solubility, human intestinal absorption, and oral bioavailability.


METHODS
Rather than giving detailed descriptions of the ADME prediction models, we focus on the discussions of the prediction accuracies of the in silico models.


CONCLUSIONS
We find that the robustness and predictive capability of the ADME models are directly associated with the complexity of the ADME property. For the ADME properties involving complex phenomena, such as bioavailability, the in silico models usually cannot give satisfactory predictions. Moreover, the lack of large and high-quality data sets also greatly hinder the reliability of ADME predictions. While considerable progress has been achieved in ADME predictions, many challenges remain to be overcome.
Hou
Tingjun
T
University of California at San Diego, Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, 9500 Gilman Drive, La Jolla, CA 92093-0359, USA. tingjunhou@hotmail.com
Wang
Junmei
J
D000284:Administration, Oral; D001682:Biological Availability; D003198:Computer Simulation; D006801:Humans; D007408:Intestinal Absorption; D008954:Models, Biological; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012995:Solubility
D004364:Pharmaceutical Preparations