Microdialysis in the study of drug transporters in the CNS

Adv Drug Deliv Rev. 2000 Dec 15;45(2-3):295-307. doi: 10.1016/s0169-409x(00)00104-6.

Abstract

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) comes 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 reports (grouped by class of compounds) where investigators have used microdialysis to examine the distribution of therapeutic agents to the CNS, and have reached conclusions regarding the functional presence of drug transporters in the brain.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Brain / metabolism*
  • Colchicine / pharmacokinetics
  • Etoposide / pharmacokinetics
  • Humans
  • Microdialysis*
  • Morphine / pharmacokinetics
  • Probenecid / pharmacology
  • Rhodamines / pharmacokinetics
  • Zidovudine / pharmacokinetics

Substances

  • Rhodamines
  • Zidovudine
  • Etoposide
  • Morphine
  • Probenecid
  • Colchicine