Pathophysiological metabolic changes associated with disease modify the proarrhythmic risk profile of drugs with potential to prolong repolarisation.
Clifford TeBayJeffrey R McArthurMelissa MangalaNicholas KerrStewart HeitmannMatthew D PerryMonique J WindleyJamie I VandenbergAdam P HillPublished in: British journal of pharmacology (2021)
Our study demonstrates how proarrhythmic risk can be exacerbated by metabolic changes and pre-existing disease. More broadly, the study acts as a blueprint for how high-throughput in vitro screening, combined with in silico simulations can help guide both preclinical screening and clinical management of patients in relation to drugs with potential to prolong repolarisation.