Drug-protein binding: a critical review of analytical tools.
The extent of drug binding to plasma proteins, determined by measuring the free active fraction, has a significant effect on the pharmacokinetics and pharmacodynamics of a drug. It is therefore highly important to estimate drug-binding ability to these macromolecules in the early stages of drug discovery and in clinical practice. Traditionally, equilibrium dialysis is used, and is presented as the reference method, but it suffers from many drawbacks. In an attempt to circumvent these, a vast array of different methods has been developed. This review focuses on the most important approaches used to characterize drug-protein binding. A description of the principle of each method with its inherent strengths and weaknesses is outlined. The binding affinity ranges, information accessibility, material consumption, and throughput are compared for each method. Finally, a discussion is included to help users choose the most suitable approach from among the wealth of methods presented.
Vuignier
Karine
K
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai E-Ansermet 30, 1211 Geneva 4, Switzerland.
Schappler
Julie
J
Veuthey
Jean-Luc
JL
Carrupt
Pierre-Alain
PA
Martel
Sophie
S
D000818:Animals; D055808:Drug Discovery; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D011506:Proteins