title: Protein binding: do we ever learn?
abstract: Although the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agents in vitro. This might explain the somewhat contradictory results obtained from different studies. Simple in vitro models which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Within in vitro test systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibiotics in vitro become even more urgent. In addition, the quantitative relationship between the effects of protein binding in vitro and in vivo needs to be established, since the physiological conditions differ. General recommendations for testing the impact of protein binding in vitro are suggested.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Zeitlinger
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.forename: Otto
authors.initials: O
authors.lastname: Cars
authors.forename: William A
authors.initials: WA
authors.lastname: Craig
authors.forename: David
authors.initials: D
authors.lastname: Andes
authors.forename: Ursula
authors.initials: U
authors.lastname: Theuretzbacher
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D011506:Proteins