Microdialysis

Microdialysis techniques have been developed to monitor changes in the chemistry of the extracellular space in living tissue. These techniques can be used for:

  • measuring drug and metabolite concentrations in the interstitial space in brain and peripheral tissues including blood;
  • continuous monitoring of neurotransmitter release to various stimuli;
  • measuring concentrations of many analytes associated with tissue damage in the CNS and in various organs.

Microdialysis techniques require the introduction of an ultrathin, semi-permeable tube, a so-called probe in the tissue (Fig. 1) The probe is connected to a precision pump, which provides a steady fl ow of a tissue-compatible fluid through the probe at a very low fl ow rate (1–5 μl/min). Open circles on Fig. 1 depict the various endogenous compounds in the extracellular fl uid or in blood; the closed circles depict exogenous compounds (drugs to be tested or calibrators for determination of the in vivo recovery) which can be delivered by the perfusion fluid.

Figure 1.:Schematic representation of a brain probe for preclinical use.

Squares represent extracellular macromolecules that may bind analytes. Smaller molecules in the tissue - including the non-protein bound fraction of drug content in the extracellular fluid - will passively diff use across the surface of the membrane and thus enter the fl ow of the perfusate, which is sampled at regular intervals and analyzed either either on- or off-line. Over the last decade in vivo microdialysis (MD) has been increasingly applied to monitor drug distribution at peripheral tissue sites and the penetration of various agents across the blood brain barrier (Zhou and Gallo, The AAPS Journal 2005, Helmy et al., Current Medicinal Chemistry 2007). Applications of MD are being explored to address specific safety issues and MD data are likely to become an important part of new drug submissions to drug regulatory agencies (Chaurasia et al., The AAPS Journal 2007).