Protein/Tissue Related Factors

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Chapter: Biopharmaceutics and Pharmacokinetics : Protein Binding of Drugs

Protein/Tissue Related Factors: Physicochemical Properties of Protein/Binding Component, Concentration of Protein/Binding Component, Number of Binding Sites on the Protein


PROTEIN/TISSUE RELATED FACTORS


Physicochemical Properties of Protein/Binding Component

Lipoproteins and adipose tissue tend to bind lipophilic drugs by dissolving them in their lipid core. The physiologic pH determines the presence of active anionic and cationic groups on the albumin molecules to bind a variety of drugs.


Concentration of Protein/Binding Component

Among the plasma proteins, binding predominantly occurs with albumin, as it is present in a higher concentration in comparison to other plasma proteins. The amount of several proteins and tissue components available for binding, changes during disease states. This effect will be discussed in the subsequent sections.


Number of Binding Sites on the Protein

Albumin has a large number of binding sites as compared to other proteins and is a high capacity binding component. Several drugs are capable of binding at more than one site on albumin, e.g. fluocloxacillin, flurbiprofen, ketoprofen, tamoxifen and dicoumarol bind to both primary and secondary sites on albumin. Indomethacin is known to bind to 3 different sites. AAG is a protein with limited binding capacity because of its low concentration and low molecular size. Though pure AAG has only one binding site for lidocaine, in presence of HSA, two binding sites have been reported which was suggested to be due to direct interaction between HSA and AAG.

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