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Pharmacokinetic Consequences of Drug Displacement from Blood and Tissue Proteins

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Summary

Displacement of one drug by another from blood and/or tissue protein will alter the pharmacokinetic behaviour of the displaced drug. For restrictively cleared drugs, displacement from blood proteins will cause only a transient change in free drug concentration and hence in pharmacodynamic response, so that dosage adjustments are rarely necessary. Total drug concentrations, however, are decreased and must be appropriately interpreted. Binding displacement from blood and/or tissue will also shorten the half-lives of these drugs, thus magnifying peak-trough differences during a dosage interval. These theoretical expectations are supported by examples of drug displacement interactions involving warfarin and phenytoin.

Although total drug concentrations in blood will be unchanged, free drug concentrations will be increased and drug response enhanced for non-restrictively cleared drugs as a result of displacement from blood protein, possibly necessitating a dosage reduction.

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  1. College of Pharmacy, Ohio State University, 217 Parks Hall, 500 West 12th Avenue, Columbus, Ohio, 43210, USA

    Janis J. MacKichan

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MacKichan, J.J. Pharmacokinetic Consequences of Drug Displacement from Blood and Tissue Proteins. Clin Pharmacokinet 9 (Suppl 1), 32–41 (1984). https://doi.org/10.2165/00003088-198400091-00005

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