Abstract
Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.
Highlights
Plasma protein binding (PPB) is a reversible process that plays a critical role in drug therapy, influencing both the pharmacokinetic and pharmacodynamic properties of drugs
These studies had an approach based on mass balance, and showed that the limitation given by the non-specific binding (NSB) can be corrected, even in the case of compounds with increased lipophilia, because NSB sites are inactivated in the presence of plasma
The experimental conditions in PPB studies are of great importance as they may greatly affect the results of the analysis [27,28]
Summary
Doctoral School of Medicine and Pharmacy, I.O.S.U.D., George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 38 Gheorghe Marinescu Street, RO-540142 Targu Mures, Romania.
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