title: Global analytical strategy to measure drug-plasma protein interactions: from high-throughput to in-depth analysis.
abstract: The selection of drug candidates with improved pharmacokinetics is essential to reduce the attrition rates during drug development and represents one of the big challenges faced by the pharmaceutical industry. Plasma protein binding (PPB) is an important parameter with significant implications for in vivo drug performance. Today, the most widely used techniques for PPB measurement in the pharmaceutical community are equilibrium dialysis (ED) and ultrafiltration (UF). However, these techniques have some limitations. Thus, we emphasize an alternative strategy, based on a global, new and easy-to-follow methodology, to screen and perform determination of PPB, using orthogonal techniques (i.e. liquid chromatography (LC), capillary electrophoresis (CE), surface plasmon resonance (SPR) based biosensor). We anticipate that the increased knowledge gained through this strategy will lead to improved drug candidates.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland. Electronic address: karine.vuignier@unige.ch.
authors.forename: Karine
authors.initials: K
authors.lastname: Vuignier
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
authors.forename: Julie
authors.initials: J
authors.lastname: Schappler
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D015195:Drug Design; D004345:Drug Industry / Q000379:methods; D019075:Electrophoresis, Capillary / Q000379:methods; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011485:Protein Binding; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D001798:Blood Proteins; D004364:Pharmaceutical Preparations