Chapter 8: Cardiac Toxicity Prediction: To Simplify, or to Integrate, that is the Question

Cardiovascular toxicity has been the bane of drug developers. Over the past decade several multibillion dollar drugs have been withdrawn from the market place for unacceptable cardiovascular toxicity. An expanding repertoire of nonclinical assays has found use in predictive cardiovascular toxicology and as aids in gaining mechanistic understanding of known cardiotoxic compounds. The use of a number of these assays as predictive tools in drug development was solidified with the development of the International Conference on Harmonisation S7A and S7B guidelines which mandate nonclinical assessment of cardiovascular effects for small molecule drugs prior to initiation of clinical trials. In this chapter, a number of in vitro assays, including ion channel binding assays, patch clamp electrophysiology, Purkinje fiber assays, Langendorff preparations and cardiomyocyte toxicity assays, are discussed.