Probe calibration in transient microdialysis in vivo

Purpose. We examine the theoretical basis for calibrating microdialysis probes in vivo for pharmacokinetic experiments in which the extracellular analyte concentrations vary in time. Methods. A software package, MICRODIAL, was used to simulate microdialysis for illustrative transient situations with linear concentration dependence. Results. For a constant distant extracellular analyte concentration, the calibration factor (extraction fraction, E-d) exhibits a mass transfer transient associated with the development of spatial concentration profiles within the tissue and the probe. Processes clearing the analyte from the extracellular fluid (ECF) strongly influence the rapidity of approach to steady-state and affect the magnitude of the steady-state calibration factor, E-d(ss). For situations in which the distant ECF concentration varies in time as a result of exchange with the plasma compartment, different time profiles of the distant ECF and plasma concentrations yield different transient E-d. For the linear, transient cases examined, the area-under-the-curve (AUC(0-infinity)) time integral of the distant ECF concentration was found to be proportional to the outflow dialysate concentration-lime integral with E-d(ss) being the proportionality constant. Conclusions. The options for calibrating microdialysis probes in solid tissues appear limited under non-steady state conditions; however, AUC integrals for linear systems may be determined by continuous microdialysis sampling and steady-state probe calibration approaches.