TY - JOUR
T1 - Pharmacogenetic issues in thorough QT trials
AU - Judson, Richard S.
AU - Salisbury, Benjamin A.
AU - Reed, Carol R.
AU - Ackerman, Michael J.
N1 - Funding Information:
Dr Ackerman’s Sudden Death Genomics Laboratory is supported by the Dr Scholl Foundation, the CJ Foundation for SIDS, the Doris Duke Charitable Foundation, the American Heart Association (Established Investigator Award), and the NIH (HD42569). Dr Ackerman is a consultant for Clinical Data. The Mayo Foundation for Medical Education and Research receives royalties from Clinical Data (formerly Genaissance Pharmaceuticals) for the intellectual property utilized in their genetic test for cardiac ion channel mutations (FAMILION™). The remaining authors have employment and/or ownership interests in Clinical Data, which in addition to offering the FAMI-LION™ test also has patent and product interests relevant to DI-LQT.
PY - 2006
Y1 - 2006
N2 - Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market.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.
AB - Drug-induced QT prolongation (DI-LQT), through its associated arrhythmias, is a leading cause of drugs being withdrawn from the market.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.
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U2 - 10.1007/BF03256454
DO - 10.1007/BF03256454
M3 - Review article
C2 - 16771601
AN - SCOPUS:33745668444
SN - 1177-1062
VL - 10
SP - 153
EP - 162
JO - Molecular Diagnosis and Therapy
JF - Molecular Diagnosis and Therapy
IS - 3
ER -