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In Vitro Early Safety Pharmacology Screening: Perspectives Related to Cardiovascular Safety

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Principles of Safety Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 229))

Abstract

In vitro screening for cardiovascular safety liabilities of novel drug candidates presents a challenge for the pharmaceutical industry. Such approaches rely on detecting pharmacologic effects on key components of complex integrated system early in drug discovery to define potential safety liabilities. Key to such studies are the concepts of hazard identification vs. risk assessment, drug specificity vs. selectivity, and an appreciation of the challenges faced when attempting to translate in vitro findings to preclinical in vivo as well as clinical effects. This chapter defines some key aspects of early safety pharmacology screening for cardiovascular liabilities, citing studies of two key depolarizing cardiac currents (fast sodium current and L-type calcium current) as examples linked to effects on cardiac conduction and repolarization.

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Authors and Affiliations

  1. AbbVie, North Chicago, IL, USA

    Gary Gintant

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  1. Gary Gintant
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Correspondence to Gary Gintant .

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Editors and Affiliations

  1. Drug Safety Sciences, Johnson & Johnson PR&D, Raritan, New Jersey, USA

    Michael K. Pugsley

  2. Cardiovascular Division, Faculty of Life Sciences & Medicine, St Thomas' Hospital, King's College London, Rayne Institute, London, United Kingdom

    Michael J Curtis

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Gintant, G. (2015). In Vitro Early Safety Pharmacology Screening: Perspectives Related to Cardiovascular Safety. In: Pugsley, M., Curtis, M. (eds) Principles of Safety Pharmacology. Handbook of Experimental Pharmacology, vol 229. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46943-9_2

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