Pharmacogenetic issues in thorough QT trials

Richard S. Judson, Benjamin A. Salisbury, Carol R. Reed, Michael John Ackerman

Research output: Contribution to journalArticle

10 Citations (Scopus)

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Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market.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.

Original languageEnglish (US)
Pages (from-to)153-162
Number of pages10
JournalMolecular Diagnosis and Therapy
Volume10
Issue number3
StatePublished - 2006

Fingerprint

Pharmacogenetics
Pharmaceutical Preparations
Genes
Cytochrome P-450 CYP3A
Long QT Syndrome
Cytochrome P-450 CYP2D6
Cardiac Arrhythmias

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Medicine(all)
  • Pharmacology

Cite this

Judson, R. S., Salisbury, B. A., Reed, C. R., & Ackerman, M. J. (2006). Pharmacogenetic issues in thorough QT trials. Molecular Diagnosis and Therapy, 10(3), 153-162.

Pharmacogenetic issues in thorough QT trials. / Judson, Richard S.; Salisbury, Benjamin A.; Reed, Carol R.; Ackerman, Michael John.

In: Molecular Diagnosis and Therapy, Vol. 10, No. 3, 2006, p. 153-162.

Research output: Contribution to journalArticle

Judson, RS, Salisbury, BA, Reed, CR & Ackerman, MJ 2006, 'Pharmacogenetic issues in thorough QT trials', Molecular Diagnosis and Therapy, vol. 10, no. 3, pp. 153-162.
Judson, Richard S. ; Salisbury, Benjamin A. ; Reed, Carol R. ; Ackerman, Michael John. / Pharmacogenetic issues in thorough QT trials. In: Molecular Diagnosis and Therapy. 2006 ; Vol. 10, No. 3. pp. 153-162.
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