Quantification of tissue distribution of antibiotics by kinetic hysteresis analysis.

Distribution of antibiotics can be described by kinetic hysteresis analysis when concentrations are measured in the serum and an extravascular sampling site. By calculating the area of the hysteresis loop (a simple formula is presented), the relative amount of drug transferred to an extravascular site can be quantified. With this approach, changes in disposition characteristics can be evaluated under various pathophysiological conditions. In addition, a specific distribution coefficient may be derived for any drug when different dose levels are studied under identical conditions. Kinetic hysteresis analysis overcomes the drawback of conventional compartment model pharmacokinetic analysis, since no simultaneous fitting of two different concentration-time courses is feasible.