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Reversible Mechanisms of Enzyme Inhibition and Resulting Clinical Significance

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Enzyme Kinetics in Drug Metabolism

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1113))

Abstract

Inhibition of a drug-metabolizing enzyme by the reversible interaction of a drug with the enzyme, thus decreasing the metabolism of another drug, is a major cause of clinically significant drug–drug interactions. This chapter defines the four reversible mechanisms of inhibition exhibited by drugs: competitive, noncompetitive, uncompetitive, and mixed competitive/noncompetitive. An in vitro procedure to determine the potential of a drug to be a reversible inhibitor is also provided. Finally, a number of examples of clinically significant drug–drug interactions resulting from reversible inhibition are described.

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Authors and Affiliations

  1. Quintiles, 5225 Exploration Drive, Indianapolis, IN, 46241, USA

    Barbara Ring & Steven A. Wrighton

  2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA

    Michael Mohutsky

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  1. Barbara Ring
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  2. Steven A. Wrighton
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  3. Michael Mohutsky
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Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA

    Swati Nagar

  2. Novartis Inst. for BioMedical Research, Cambridge, Massachusetts, USA

    Upendra A. Argikar

  3. Drug Metabolism, Boehringer Ingelheim, Ridgefield, Connecticut, USA

    Donald J. Tweedie

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Ring, B., Wrighton, S.A., Mohutsky, M. (2014). Reversible Mechanisms of Enzyme Inhibition and Resulting Clinical Significance. In: Nagar, S., Argikar, U., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 1113. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-758-7_4

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  • DOI: https://doi.org/10.1007/978-1-62703-758-7_4

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