Pharmacokinetic considerations for the setting of in-vitro models

Nearly all in-vitro kinetic models hitherto employed only consider serum concentration curves of the antibiotic. Data thus obtained at best reflect the situation in septicaemia. However, they are not applicable for infections where infecting bacteria are not localized within the blood. This paper presents a method for calculating the time course of the non-protein bound drug in tissue water. The concept makes use of serum concentration curves, the extent of serum protein binding and the peak time of total drug concentration in the tissue. This is practicable since all data necessary for calculation are available experimentally. Using cefmenoxime, cefotaxime, latamoxef (moxalactam) and ceftriaxone as examples, the vast differences between the total concentration of the antibiotic in serum and the concentration of the non-protein bound antibiotic in the tissue water are demonstrated. Therefore, only the results of in-vitro experiments, which are based on time courses of the non-protein bound drug in the tissue water, are considered relevant for assessing therapeutic efficacy of an antibiotic.