Antimicrobial tissue concentrations

The most common pharmacokinetic and pharmacodynamic approaches for anti-infective agents rely on plasma concentration as the pharmacokinetic input value and minimum inhibitory concentration as the pharmacodynamic input value. This approach assumes that the plasma concentration is a good indicator of the respective concentrations at the infection site. This assumption, however, frequently is not correct. Furthermore, it has been shown that protein binding affects antimicrobial activity in a way that only free, unbound anti-infective compounds are pharmacologically active. Only the free tissue concentrations of antibiotics at the target site are responsible for therapeutic effect. Using total plasma concentrations frequently overestimates the target site concentrations and clinical efficacy. Microdialysis is a reliable technique that allows direct measurement of unbound tissue concentrations.