Protein Binding: Do We Ever Learn?

Abstract

ABSTRACTAlthough 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 agentsin vitro. This might explain the somewhat contradictory results obtained from different studies. Simplein vitromodels 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. Withinin vitrotest 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 antibioticsin vitrobecome even more urgent. In addition, the quantitative relationship between the effects of protein bindingin vitroandin vivoneeds to be established, since the physiological conditions differ. General recommendations for testing the impact of protein bindingin vitroare suggested.