Authors: Cavero, Icilio; Crumb, William

Source: Expert Opinion on Drug Safety, Volume 5, Number 1, 1 January 2006 , pp. 181-185(5)

Publisher: Informa Healthcare

Abstract:

This report summarises selected presentations delivered at the Safety Pharmacology Society annual meeting. Organ safety was covered, with cardiac QT liability being discussed most extensively. Of particular interest, was the lecture on beat-to-beat variability of cardiac repolarisation in anesthetised dogs with chronic atrioventricular block. This model, characterised by an electrophisyologically remodelled heart (replicating a human heart with reduced cardiac repolarisation reserve), was developed to assess the potential of drugs to cause unsafe QT prolongation that may spontaneously evolve into life-threatening arrhythmias. An interesting case study illustrated the apparent failure of safety pharmacology studies to accurately predict clinical QT liability due to an underestimated plasma concentration for therapeutic efficacy at early nonclinical stage. An emerging attractive new technology, presented as a means to minimise drug failure to reach marketing stage (attrition) dealt with biological fingerprinting which consists in placing drug candidates in the context of chemical, pharmacological, toxicological and clinical liability spaces available for marketed, withdrawn or failed drugs, as well as reference compounds. The meeting was an excellent occasion for sharing knowledge and technologies among members of this young society actively engaged in promoting safety pharmacology, a novel research activity which now plays a pivotal role in the drug development process.

Keywords: arrhythmia; beat-to-beat variability; biological fingerprint; cardiac repolarisation; cardiac safety index; QT liability; safety pharmacology; Torsades de Pointes (TdP)

Document Type: Meeting report

DOI: http://dx.doi.org/10.1517/14740338.5.1.181

Publication date: 2006-01-01

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