QT Prolongation and Oncology Drug Development.

نویسندگان

  • Michael G Fradley
  • Javid Moslehi
چکیده

Many pharmaceutical agents interact with cardiac ion channels resulting in abnormal ventricular repolarization and prolongation of the QT interval. In rare circumstances, this has resulted in the development of the potentially life-threatening arrhythmia, torsades de pointes. It is recognized, however, that accurate measurement of the QT interval is challenging, and it is a poor predictor for the development of this arrhythmia. Nevertheless, QT interval monitoring is an essential part of pharmaceutical development, and significant increases in the QT interval may prevent a drug from gaining approval.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice.

There has been an increasing focus on drug induced QT prolongation including research on drug development and QT prolongation, following the removal of drugs due to torsades de pointes (TdP). Although this has improved our understanding of drug-induced QT prolongation there has been much less research aimed at helping clinicians assess risk in individual patients with drug induced QT prolongati...

متن کامل

Predicting QT prolongation in humans during early drug development using hERG inhibition and an anaesthetized guinea-pig model

BACKGROUND AND PURPOSE Drug-induced prolongation of the QT interval can lead to torsade de pointes, a life-threatening ventricular arrhythmia. Finding appropriate assays from among the plethora of options available to predict reliably this serious adverse effect in humans remains a challenging issue for the discovery and development of drugs. The purpose of the present study was to develop and ...

متن کامل

QT Interval Prolongation as a Biomarker for Torsades de Pointes and Sudden Death in Drug Development

Prolongation of the QT interval on the surface 12-lead electrocardiogram is widely accepted as a biomarker for the potential of a drug to produce torsades de pointes and/or sudden death. Detection of drug-induced prolongation of the QT interval in animals and man is frequently confounded by extrinsic and intrinsic factors that limit the ability to detect a true drug effect. In particular drugs ...

متن کامل

Drug induced QT prolongation.

The drug-induced QT prolongation predisposes to development of torsades de pointes (TdP) ventricular tachycardia and sudden death. The association between specific drug and development of TdP is difficult to document, therefore, QT prolongation is considered as a surrogate marker of the proarrhythmia risk. Most of the drugs prolong QT interval usually by blocking the potassium IKr current or al...

متن کامل

Key clinical considerations for demonstrating the utility of preclinical models to predict clinical drug-induced torsades de pointes.

While the QT/QTc interval is currently the best available clinical surrogate for the development of drug-induced torsades de pointes, it is overall an imperfect biomarker. In addition to low specificity for predicting arrhythmias, other issues relevant to using QT as a biomarker include (1) an apparent dissociation, for some drugs (for example, amiodarone, sodium pentobarbital, ranolazine) betw...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cardiac electrophysiology clinics

دوره 7 2  شماره 

صفحات  -

تاریخ انتشار 2015