Molecular Diagnosis & Therapy

, Volume 10, Issue 3, pp 153–162

Pharmacogenetic Issues in Thorough QT Trials

  • Richard S. Judson
  • Benjamin A. Salisbury
  • Carol R. Reed
  • Michael J. Ackerman
Pharmacogenomics

DOI: 10.1007/BF03256454

Cite this article as:
Judson, R.S., Salisbury, B.A., Reed, C.R. et al. Mol Diag Ther (2006) 10: 153. doi:10.1007/BF03256454

Abstract

Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market. As a consequence, the US FDA and other regulatory agencies are mandating that all new drugs go through a so-called ‘Thorough QT’ (TQT) study to evaluate the potential for ‘QT liability’, specifically the potential for a drug to cause a discernible increase in the QT interval. Several genetic factors that modulate the risk of DI-LQT have been discovered. These are genes responsible for the congenital long QT syndrome, drug metabolism genes (mainly CYP2D6 and CYP3A4), and genes in other regulatory pathways. Here, we briefly review the links between genetic variants and drug-induced QT risk, and propose approaches to consider for using pharmacogenetics in planning and analyzing TQT studies.

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Richard S. Judson
    • 1
  • Benjamin A. Salisbury
    • 2
  • Carol R. Reed
    • 2
  • Michael J. Ackerman
    • 3
  1. 1.SpyroPharmaGuilfordUSA
  2. 2.Clinical Data, Inc.New HavenUSA
  3. 3.Sudden Death Genomics LaboratoryMayo Clinic College of MedicineRochesterUSA
  4. 4.Genaissance Pharmaceuticalsa Clinical Data, Inc. CompanyNew HavenUSA