Application of basic pharmacokinetic concepts to analysis of microdialysis data: illustration with imipenem muscle distribution

Abstract

Background: Microdialysis studies of antibacterial tissue distribution in critically ill patients have sometimes led to results that were spectacular but inconsistent with basic pharmacokinetic concepts.

Objective: To conduct a study of imipenem distribution in the muscle of healthy volunteers and critical care patients in order to compare real-life data with theory.

Methods: Microdialysis catheters were placed into the quadriceps, and probe recoveries were determined individually in vivo using a retrodialysis-by-drug method. Unbound imipenem concentrations were determined by high-performance liquid chromatography in plasma ultrafiltrates and muscle dialysates, and submitted to noncompartmental pharmacokinetic analysis.

Results: Individual unbound imipenem concentrations in plasma and muscle extracellular fluid were virtually superimposed at any time, both in healthy volunteers and in critical care patients.

Conclusion: These new results are not consistent with previously published data obtained in similar conditions by another group, but they are in agreement with results previously obtained in rats, as well as being consistent with basic pharmacokinetic concepts.