%0 Journal Article
%T e-PKGene: A knowledge-based research tool for analysing the impact of genetics on drug exposure
%A Houda Hachad
%A Casey Overby
%A Sophie Argon
%A Catherine K Yeung
%A Isabelle Ragueneau-Majlessi
%A Ren¨¦ H Levy
%J Human Genomics
%D 2011
%I BioMed Central
%R 10.1186/1479-7364-5-5-506
%X Differences in drug response among patients are common, often leading to challenges in optimising a dosage regimen for an individual patient. Genetic factors have long been known to cause interindividual differences in the pharmacokinetics, efficacy and adverse events of a number of drugs,[1] and drug metabolising enzymes have been shown to be the greatest source of pharmacogenetic (PGx) variability identified to date. It is estimated that over half of the ~170 genes with products affecting drug disposition are polymorphic,[2] and clinically important polymorphisms have been identified for most major enzymes involved in both phase I and phase II drug metabolism [3]. More recently, the polymorphic variability of several transporter proteins, such as the hepatic uptake transporter, organic anion transporter polypeptide 1B1 (OATP1B1), has been shown to have an impact on the exposure to, and safety of, widely prescribed drugs [4]. Thus, incorporating the knowledge gained from PGx research to make decisions in drug development and clinical care has the potential to increase the safety and efficacy of drug treatment, and is central to the strategies of personalised medicine [5]. In spite of current efforts to incorporate the use of PGx information in drug development, clinical practice and in making cost-effective healthcare decisions, however, information uptake remains low. Translational research is required to move PGx discoveries effectively to evidence-based application in these areas. Translational research has been described as having four iterative phases with feedback loops, to allow integration of new knowledge [6]. Phase 1 (T1) and Phase 2 (T2) translational research informs the development of clinical interventions and evidence-based guidelines; Phase 3 (T3) research assesses the implementation of guidelines in health practice; and Phase 4 (T4) research evaluates the health outcomes of changes in practice following the implementation of guidelines [6]. All pha
%K Database
%K pharmacogenetics
%K metabolism
%K transporters
%K cytochrome P450 enzymes
%U http://www.humgenomics.com/content/5/5/506