The Role of ADME Pharmacogenomics in Early Clinical Trials: Perspective of the Industry Pharmacogenomics Working Group (I-PWG)

Abstract

Genetic polymorphisms in metabolizing enzymes and drug transporters have been shown to significantly impact the exposure of drugs having a high dependence on a single mechanism for their absorption, distribution or clearance, such that genotyping can lead to actionable steps in disease treatment. Recently, global regulatory agencies have provided guidance for assessment of pharmacogenomics during early stages of drug development, both in the form of formal guidance and perspectives published in scientific journals. The Industry Pharmacogenomics Working Group (I-PWG), conducted a survey among member companies to assess the practices relating to absorption, distribution, metabolism, excretion pharmacogenomics) during early stages of clinical development, to assess the impact of the recent Regulatory Guidance issued by the US FDA and EMA on Industry practices.

Keywords::

• absorption, distribution, metabolism and excretion
• ADME
• drug metabolism
• drug transporters
• pharmacogenomics
• pharmacokinetics
• Regulatory Guidance

Financial & competing interests disclosure

L Tremaine and J-C Marshall are employees of Pfizer Inc., W Brian and K Pearson are employees of are employees of Sanofi, T DelMonte is an employee of Bristol Myer Squib, S Francke is an employee of Janssen Research and Development, P Groenen is an employee of Actelion Pharmaceuticals Ltd., K Johnson and L Li are former employees of Novartis Institutes for Bio Medical Research. All authors have stock in their companies. The authors have no other 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 apart from those disclosed.

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