On the calculation of the concentration dependence of drug binding to plasma proteins with multiple binding sites of different affinities: Determination of the possible variation of the unbound drug fraction and calculation of the number of binding sites of the protein
Leonid M. Berezhkovskiy;
Published: 18 Oct 2006 Journal: Journal of Pharmaceutical Sciences, volume 96, pages 249-257 (issn: 0022-3549, Copyright policy)
The measurement of the unbound drug fraction in plasma is routinely performed at drug concentrations much less than that of plasma proteins. Commonly, the protein has several binding sites of different affinities. The obtained value of the unbound drug fraction does not yield the affinity of each binding site separately. For drug binding to a single type of protein, it is shown that the assumption that all binding sites of the protein have the same affinity yields the slowest possible concentration increase of the unbound drug fraction, while the assumption that a drug binds to a single binding site yields the highest possible value of the unbound fraction for a...