Key result
The Safety Pharmacology Society annual meeting highlighted advances in assessing cardiac QT liability, including a novel dog model and biological fingerprinting to minimize drug attrition.
The 5th Annual Meeting of the Safety Pharmacology Society highlighted advancements in preclinical models for assessing cardiac QT liability and new technologies to minimize drug attrition.
Novel QT models may refine early safety screening; leaves open clinical translation and attrition impact pending validation.
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in the context of chemical, pharmacological, toxicological and clinical liability spaces available for marketed, withdrawn or failed drugs, as well as reference compounds.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.
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Cavero et al. (2005) studied Cardiac QT liability. The Safety Pharmacology Society annual meeting highlighted advances in assessing cardiac QT liability, including a novel dog model and biological fingerprinting to minimize drug attrition.
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