Microdialysis for pharmacokinetic analysis of drug transport to the brain

The intracerebral microdialysis technique represents an important tool for monitoring free drug concentrations in brain extracellular fluid (brain(EcF )) as a function of time. With knowledge of associated free plasma concentr ations, it provides information on blood-brain barrier (BBB) drug transport . However, as the implantation of the microdialysis probe evokes tissue rea ctions, it should be established if the BBB characteristics are maintained under particular microdialysis experimental conditions. Several studies hav e been performed to evaluate the use of intracerebral microdialysis as a te chnique to measure drug transport across the BBB and to measure regional ph armacokinetics of drugs in the brain. Under carefully controlled conditions , the intracerebral microdialysis data did reflect passive BBB transport un der normal conditions, as well as changes induced by hyperosmolar opening o r by the presence of a tumor in the brain. Studies on active BBB transport by the mdr1a-encoded P-glycoprotein (Pgp) were performed, comparing mdr1a(- /-) with wild-type mice. Microdialysis surgery and experimental procedures did not affect Pgp functionality, but the latter did influence in vivo conc entration recovery, which was in line with theoretical predictions. It is c oncluded that intracerebral microdialysis provides meaningful data on drug transport to the brain, only if appropriate methods are applied to determin e in vivo concentration recovery. (C) 1999 Elsevier Science B.V. All rights reserved.