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QT-screen: high-throughput cardiac safety pharmacology by extracellular electrophysiology on primary cardiac myocytes. | LitMetric

QT-screen: high-throughput cardiac safety pharmacology by extracellular electrophysiology on primary cardiac myocytes.

Assay Drug Dev Technol

Multi Channel Systems MCS GmbH, Aspenhaustrasse 21, 72770 Reutlingen, Germany.

Published: October 2004

AI Article Synopsis

  • Cardiac safety pharmacology primarily concerns drug-induced QT interval prolongation on the electrocardiogram, which indicates a higher risk for severe ventricular arrhythmias.
  • To mitigate financial losses during drug development, guidelines require QT prolongation safety tests to be conducted early in vitro and in vivo before clinical trials.
  • The QT-Screen system utilizes primary cardiac myocytes to provide efficient, high-throughput screening, enabling the assessment of over 100 compounds daily, yielding approximately 6,000 data points at a low cost per data point, while also allowing for adaptation to good laboratory practice settings.

Article Abstract

Cardiac safety pharmacology focuses mostly on the drug-induced prolongation of the QT interval in the electrocardiogram. A prolonged QT interval is an important indicator for an increased risk of severe ventricular arrhythmia. Guidelines demand safety tests addressing QT prolongation in vitro and in vivo before a drug enters clinical trials. If safety risks will be detected not until an advanced stage of preclinical drug development, a considerable sum of money has already been invested into the drug development process. To prevent this, high-throughput systems have been developed to obtain information on the potential toxicity of a substance earlier. We will discuss in this publication that the QT-Screen system, which is based on primary cardiac myocytes, is able to provide a sufficient throughput for secondary screening. With this system, extracellular field potentials can be recorded from spontaneously beating cultures of mammalian or avian ventricular cardiac myocytes simultaneously on 96 channels. The system includes software-controlled and automated eight-channel liquid handling, data acquisition, and analysis. These features allow a user-friendly and unsupervised operation. The throughput is over 100 compounds in six replicates and with full dose-response relationships per day. This equals a maximum of approximately 6,000 data points per day at an average cost for consumables of 0.20 US pennies (U.S.) per data point. The system is intended for a non-good laboratory practice-compliant screening; however, it can be adapted to be used in a good laboratory practice environment.

Download full-text PDF

Source
http://dx.doi.org/10.1089/adt.2004.2.507DOI Listing

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