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Protein Binding

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Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Incorporation of pharmacokinetic information of anticancer drugs into routine patient care can contribute to drug dosage individualization and account for differences among patients in rates of drug metabolism and/or excretion. The standard analytical methods for measuring concentrations of drugs in plasma determine drug bound to plasma proteins as well as free drug dissolved in plasma water. For this reason, the relationship between total drug concentration in plasma and treatment outcome (i.e., toxicity and efficacy) will only be good if the degree of plasma protein binding of the agent is constant, or if so little drug is protein bound that changes in binding make insignificant changes in unbound concentration. A review of available literature data indicates that, in general, protein binding of anticancer drugs is not of principal clinical relevance. However, there are several instances in which monitoring of unbound concentrations might be useful: (1) agents demonstrating protein concentration-dependent binding, (2) agents that bind irreversible or near covalently, (3) when formulation excipients modulate unbound drug levels, and (4) metabolically interconversible agents. While available evidence suggests that for these agents unbound drug levels correlate better with clinical effects than total plasma concentrations, there are insufficient data to justify the recommendation of the routine use of unbound drug concentration monitoring for most of these agents at present.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 313, CCC Room I5308, Memphis, TN, USA

    Alex Sparreboom Ph.D.

  2. Department of Medical Oncology, Laboratory of Translational and Molecular Pharmacology, Erasmus MC – Daniel den Hoed Cancer Center, Tiofarma B.V., 3260 BB, Oud-Beijerland, The Netherlands

    Walter J. Loos Ph.D.

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  1. Alex Sparreboom Ph.D.
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  2. Walter J. Loos Ph.D.
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Correspondence to Alex Sparreboom Ph.D. .

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Editors and Affiliations

  1. Sidney Kimmel Comprehensive Cancer Cente, Baltimore, Maryland, USA

    Michelle A. Rudek

  2. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    Cindy H. Chau

  3. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    William D. Figg

  4. Moffitt Cancer Center, Tampa, Florida, USA

    Howard L. McLeod

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Sparreboom, A., Loos, W.J. (2014). Protein Binding. In: Rudek, M., Chau, C., Figg, W., McLeod, H. (eds) Handbook of Anticancer Pharmacokinetics and Pharmacodynamics. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9135-4_13

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