Plasma protein binding (PPB) is known to significantly influence tissue penetration, biological half-life and the volume of distribution of antimicrobial substances. Generally PPB reduces the free fraction of a drug since only the unbound fraction is pharmacologically active. Furthermore, the impact of PPB on the antimicrobial effects of antibiotics has been investigated by several in vitro studies. Most of the data are collected from methods which use the minimal inhibitory concentration (MIC). The MIC does not represent bactericidal activity nor can it deliver information on the time versus killing course of an antibiotic. In contrast, time-killing curves provide the opportunity to compare growth curves and killing curves and are therefore often used for the exploration of the impact of PPB on antimicrobial activity.
This paper is set out to summarize methods for the quantification of protein binding, microbiological growth media for the determination of the impact of protein binding on antimicrobial activity of antibiotics and various pharmacodynamic in vitro studies that are used in this context. The advantages and disadvantages of these approaches will be described and compared.