Assessment of Drug Metabolism Enzyme and Transporter Pharmacogenetics in Drug Discovery and Early Development: Perspectives of the I-Pwg

Abstract

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
• pharmacokinetic variability
• pharmacogenetics
• polymorphism
• reaction phenotyping

To view the supplementary data that accompany this paper,please visit the journal website at: www.futuremedicine.com/doi/full/10.2217/pgs.16.9

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.