Assessment of drug metabolism enzyme and transporter pharmacogenetics in drug discovery and early development: perspectives of the I-PWG

Pharmacogenomics. 2016 Apr;17(6):615-31. doi: 10.2217/pgs.16.9. Epub 2016 Apr 5.


Genetic variants of drug metabolism enzymes and transporters can result in high pharmacokinetic and pharmacodynamic variability, unwanted characteristics of efficacious and safe drugs. Ideally, the contributions of these enzymes and transporters to drug disposition can be predicted from in vitro experiments and in silico modeling in discovery or early development, and then be utilized during clinical development. Recently, regulatory agencies have provided guidance on the preclinical investigation of pharmacogenetics, for application to clinical drug development. This white paper summarizes the results of an industry survey conducted by the Industry Pharmacogenomics Working Group on current practice and challenges with using in vitro systems and in silico models to understand pharmacogenetic causes of variability in drug disposition.

Keywords: drug metabolism enzyme; drug transporter; modeling; pharmacogenetics; pharmacokinetic variability; polymorphism; reaction phenotyping.

Publication types

  • Review

MeSH terms

  • Drug Discovery / methods
  • Genetic Variation / genetics*
  • Humans
  • Inactivation, Metabolic / genetics*
  • Membrane Transport Proteins / genetics*
  • Pharmacogenetics / methods


  • Membrane Transport Proteins