title: Development of a broad-based ADME panel for use in pharmacogenomic studies.
abstract: OBJECTIVE
  To optimally address the interindividual variability observed in pharmacokinetic drug response, we have created a custom genotyping panel that interrogates most of the key genetic variations present in a set of 181 prioritized genes responsible for the absorption, distribution, metabolism and excretion (ADME) of many therapeutic agents. This consensus list of genes and variants was based on the ADME core and extended gene lists compiled by a group of pharmaceutical companies as having relevance. Although these pharmacokinetic genes and pathways are well known, tools that can interrogate a large number of these genes simultaneously within a single experiment are not currently available.
  
  
  METHODS
  Using novel design strategies, we have developed an optimized and validated ADME genotyping panel, encompassing approximately 3000 variants, that has broad applicability to any study or clinical trial that would benefit from the evaluation of an extensive list of ADME genes.
  
  
  CONCLUSIONS
  Over the course of three design iterations, overall assay conversion rates were improved from 83 to 97% resulting in a panel that fills in many of the gaps in coverage present on currently available commercial genotyping assays. The utility of the assay has been demonstrated by the screening of more than 1000 samples resulting in the discovery of novel pharmacogenomic associations. The assay, and the underlying methods, will continue to be a valuable tool for use in future pharmacogenomic studies.
authors.affiliation: Beaulieu-Saucier Université de Montréal Pharmacogenomics Centre, Montréal, QC, Canada.
authors.forename: Andrew M K
authors.initials: AM
authors.lastname: Brown
authors.forename: Yannick
authors.initials: Y
authors.lastname: Renaud
authors.forename: Colin
authors.initials: C
authors.lastname: Ross
authors.forename: Mark
authors.initials: M
authors.lastname: Hansen
authors.forename: Ian
authors.initials: I
authors.lastname: Mongrain
authors.forename: Diane
authors.initials: D
authors.lastname: Valois
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Michael S
authors.initials: MS
authors.lastname: Phillips
mesh_terms: D002986:Clinical Trials as Topic; D005838:Genotype; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods*; D010599:Pharmacokinetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D004364:Pharmaceutical Preparations
keywords: ADME; SNPs; drug metabolism; genotyping; pharmacogenomics