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Drug Binding in Plasma

A Summary of Recent Trends in the Study of Drug and Hormone Binding

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  • Clinical Pharmacokinetic Concepts
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Summary

The ligands are generally bound in plasma to a significant extent by several transport proteins (both high and low affinity), irrespective of their endogenous or exogenous origin. The protein binding of endogenous compounds (such as hormones) exhibits higher affinity and specificity than those of exogenous compounds (such as drugs). For plasma proteins that bind the same ligand(s), structural similarities or a common genetic origin may be found, although this is not a general rule. Alterations in ligand binding may be due to modifications of either the structure or the level of the binding protein. These modifications may result from genetic make up, physiology or pathology. In some situations, plasma binding may impair the distribution of drugs to tissues, with drug distribution then mainly restricted to the distribution compartment of the drug-binding protein. In other instances, the plasma drug-binding is permissive, and does not limit drug distribution to tissues. A given drug-transport protein system may have either a permissive or a restrictive effect on the drug distribution, depending on the tissue.

The physiological significance of the high-affinity transport proteins is not completely understood. These proteins may increase the plasma concentration of poorly hydrosoluble ligands, ensure a more uniform tissue distribution and increase the life of the ligands. The life of the protein may also be increased by ligand binding. High-affinity transport proteins are also involved in some specific carrier mediated transfer mechanisms. It is possible to demonstrate structure-binding relationships or binding selectivity for the plasma transport proteins, but these are quite independent of relationships observed at the receptor level.

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  1. Centre Hospitalier Intercommunal, Laboratoire Hospitalo-Universitaire de Pharmacologie de l’Université Paris XII, 40, Avenue de Verdun, F-94010, Créteil, France

    Françoise Hervé, Saïk Urien, Edith Albengres, Jean-Claude Duché &  Jean-Paul Tillement

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Hervé, F., Urien, S., Albengres, E. et al. Drug Binding in Plasma. Clin. Pharmacokinet. 26, 44–58 (1994). https://doi.org/10.2165/00003088-199426010-00004

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