Evolution of ADME Science: Where Else Can Modeling and Simulation Contribute?

• Published in: Molecular pharmaceutics Vol. 10; no. 4; pp. 1162 - 1170
• Main Author: Smith, Dennis A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.04.2013
• Subjects: Chemistry, Pharmaceutical - methods; Chemistry, Physical - methods; Computer Simulation; Drug Design; Drug Discovery - methods; Hepatocytes - drug effects; Humans; Microsomes, Liver - drug effects; Models, Theoretical; Reproducibility of Results; Software; Structure-Activity Relationship; transporters; CYP450; hepatotoxicity; permeability; antibody−drug conjugates; TPSA; metabolites; PSA
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp3005319

The commentary describes progress in modeling and simulation in ADME science and focuses on lipoidal permeability as a central driver of drug molecule disposition. The tension between screening and in silico is outlined with practical suggestions on how to improve multiparameter models. The limitations on modeling drug metabolism and its enzymes are highlighted together with key features in molecules that lead to drug transport. Reservations about the quality of data and the imprecise classification of drug molecules are explained. Encouragement to move modeling and simulation to the forefront of project start-up is provided after examining the complexity of macromolecule-small molecule conjugate prodrugs.