Compilation of 222 drugs’ plasma protein binding data and guidance for study designs

The binding of a drug to plasma protein reduces free drug in the blood circulation that would otherwise be available for penetration into tissues to reach the therapeutic target or the kidney for elimination. Therefore, the binding event affects drug elimination from the body, efficacy, duration of action and toxicity. Co-administration of other drugs, food and pathological conditions of patients can significantly change percentage binding of the drug and result in serious consequences. Here, we present the largest and newest information on plasma protein binding for 222 drugs, of which 50% show 90–100% binding, a range that could be considered as a favorable element for future lead selection. We also provide critical and comprehensive evaluations on the methods and techniques established to determine plasma protein binding, pinpoint advantages and pitfalls of individual approaches, and offer detailed guidance for experimental designs, including ultrafiltration, equilibrium dialysis, ultracentrifugation, charcoal adsorption, high-performance affinity chromatography, high-performance frontal analysis, solid-phase microextraction and in vivo microdialysis.