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Cardiac Safety of Noncardiac Drugs pp 83–103Cite as

Pharmacogenomics in Drug Development

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Abstract

Pharmacogenomics research typically aims to find genetic variants that affect the pharmacokinetics or the pharmacodynamics of a drug. Pharmacokinetic effects can be very direct, and are therefore easy to understand. Genetic variants can cause loss of function for a metabolic enzyme that can in turn decrease the rate at which a drug is metabolized. This increases the amount of drug delivered to the active site, as well as the half-life of the drug in the system. There is a wider range of pharmacodynamic effects. A variant can change the binding properties of a receptor to which a drug is targeted, and can therefore affect activity. Alternatively, a variant can simply alter the level of expression of some protein that can lead to an indirect effect on drug action. Variants that cause such expression changes can be cis, meaning that a variant in the gene has a direct effect on the gene’s expression level. Alternatively, the effect can be trans, meaning that variation elsewhere in the genome indirectly affects expression levels for the gene. Genes causing such trans effects can be far removed from pathways directly involved in drug action.

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Author information

Authors and Affiliations

  1. Research & Development, Genaissance Pharmaceuticals, New Haven, CT, USA

    Richard Judson PhD (Chief Scientific Officer, Senior Vice President)

  2. University of Rochester Medical Center, Rochester, NY, USA

    Arthur J. Moss MD, FACC (Professor of Medicine (Cardiology), Director of Hear Research Follow-Up Program)

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  1. Richard Judson PhD
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Editor information

Editors and Affiliations

  1. eResearchTechnology Inc., Philadelphia, PA, USA

    Joel Morganroth MD (Chief Scientist, Clinical Professor of Medicine) (Chief Scientist, Clinical Professor of Medicine)

  2. University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Joel Morganroth MD (Chief Scientist, Clinical Professor of Medicine) (Chief Scientist, Clinical Professor of Medicine)

  3. Global Medical Affairs, eResearchTechnology Inc., Bridgewater, NJ

    Ihor Gussak MD, PhD, FACC (Vice President, Clinical Associate Professor of Medicine, Associate Editor) (Vice President, Clinical Associate Professor of Medicine, Associate Editor)

  4. UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ

    Ihor Gussak MD, PhD, FACC (Vice President, Clinical Associate Professor of Medicine, Associate Editor) (Vice President, Clinical Associate Professor of Medicine, Associate Editor)

  5. Journal of Electrocardiology, Bridgewater, NJ, USA

    Ihor Gussak MD, PhD, FACC (Vice President, Clinical Associate Professor of Medicine, Associate Editor) (Vice President, Clinical Associate Professor of Medicine, Associate Editor)

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© 2005 Humana Press Inc., Totowa, NJ

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Judson, R., Moss, A.J. (2005). Pharmacogenomics in Drug Development. In: Morganroth, J., Gussak, I. (eds) Cardiac Safety of Noncardiac Drugs. Humana Press. https://doi.org/10.1007/978-1-59259-884-7_5

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