Pharmacogenetic issues in thorough QT trials
Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market.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 t...
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| Veröffentlicht in: | Molecular diagnosis & therapy 2006-01, Vol.10 (3), p.153-162 |
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| container_title | Molecular diagnosis & therapy |
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| creator | Judson, Richard S Salisbury, Benjamin A Reed, Carol R Ackerman, Michael J |
| description | Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market.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. |
| doi_str_mv | 10.1007/BF03256454 |
| format | Article |
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| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Arrhythmias, Cardiac - chemically induced Arrhythmias, Cardiac - complications Arrhythmias, Cardiac - genetics Clinical Trials as Topic Cytochrome P-450 CYP2D6 - genetics Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - genetics Drug-Related Side Effects and Adverse Reactions Humans Long QT Syndrome - chemically induced Long QT Syndrome - complications Long QT Syndrome - genetics Pharmacogenetics Torsades de Pointes - chemically induced Torsades de Pointes - genetics |
| title | Pharmacogenetic issues in thorough QT trials |
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