Studies on Drug – Human Serum Albumin Binding: The Current State of the Matter

Abstract

Human serum albumin (HSA) is the major plasma protein with vital functions acting as depot and career for many endogenous (fatty acids, bilirubin, etc.) and exogenous substances (drugs, nutrients, etc.) in the blood. Binding to HSA controls the free, active concentration of the drug and may affect considerably the overall pharmacodynamic and pharmacokinetic profile. Studies on drug - protein binding are important from both theoretical and practical point of view as they allow better understanding of the processes underlying drug disposition and elimination and the effect of several pathological states or co-administered drugs on drug delivery and efficacy. The present review focuses on the current state of drug - HSA binding studies. The major functions and consequences of drug - protein binding are described. The X-ray structure of HSA is discussed focusing on the location and the architecture of the primary drug and fatty acids binding sites. Some of the most commonly used methods for drug - HSA binding assay are presented together with examples for their application. The most extensive studied topics in the area are discussed including quantitative characterization of drug - HSA complexation, identification of the binding sites, stereoselectivity of drug - HSA interactions, and thermodynamic characterization of the binding process. A short section is devoted to in silico prediction of drug - HSA binding as an important step in drug design and development.

Glycated Serum Albumin and AGE Receptors

“…Serum albumin has numerous binding sites for endogenous ligands, transition metals, and small drug molecules. The two major drug-binding sites are Sudlow site I and site II [170][171][172], but other sites for drug binding exist as well [173,174]. Drug binding to GA has been investigated for several drugs, including warfarin [175][176][177], acetohexamide [178], tolbutamide [179], phenylbutazone [180], diclofenac [181], captopril [182], diazepam [183], ketoprofen [130,184], and others.…”

Tactics for preclinical validation of receptor-binding radiotracers

“…Radiopharmaceutical lipophilicity is a major contributor to the weak interactions [128], and albumin is the chief target since it makes up about half of the total protein in human serum. There are two primary, and multiple secondary, binding sites for drugs on human serum albumin [130,131]. Species differences are well known for the binding of radiopharmaceuticals to human and animal serum albumins, a factor that should be kept in mind when attempting to extrapolate results from one species to another [132].…”

“…A variety of in vitro methods, each with experimental caveats, can be used to assess serum or plasma protein binding. These include equilibrium dialysis, ultrafiltration, ultracentrifugation and precipitation assays [126,131,133]. The 2,2,2-trichloroacetic acid (TCA) protein precipitation assay is a simple way to evaluate plasma protein binding.…”

In vitro Analysis of the Interaction between Human Serum Albumin and Semi‑Synthetic Clerodanes

“…In other words, studies on albumin-drug binding are important from both theoretical and practical point of view as they allow better understanding of processes underlying drug disposition and elimination, as well as the effect of several pathological states or co-administered drugs on delivery and efficacy. 4 Croton cajucara Benth (Euphorbiaceae), popularly known as "sacaca", is a widely grown tree of the Amazon region, North of Brazil, used in folk medicine. 5 The norclerodane trans-dehydrocrotonin (t-DCTN, Figure 1) is the main diterpene present in Croton cajucara.…”