Quantitative microdialysis in the central nervous system (CNS) has recently
provided evidence for the existence of transporters as they relate to the
brain distribution of a variety of drugs. Support for the existence of drug
transporters in the blood-brain barrier (or in the blood-CSF barrier) come
s from investigations that have found: unbound drug concentrations in brain
fluids that are lower than corresponding levels in plasma; saturability of
transport clearances across the blood-brain barrier and; the regulation of
transport by putative inhibitors. Additional confirmatory evidence for the
existence of active transport or carrier-mediated processes has also been
derived from models that relate observed drug levels in the CNS with those
in plasma or blood. The conclusion that reduced drug levels in brain fluids
generally indicate the existence of active efflux transport is questioned.
In the case of relatively polar compounds with modest blood-brain barrier
permeability, lower unbound concentrations in brain may be a consequence of
dilution by turnover of brain fluids. This review summarizes recent report
s (grouped by class of compounds) where investigators have used microdialys
is to examine the distribution of therapeutic agents to the CNS, and have r
eached conclusions regarding the functional presence of drug transporters i
n the brain. (C) 2000 Elsevier Science B.V. All rights reserved.