Microdialysis in the study of drug transporters in the CNS

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...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2000-12, Vol.45 (2), p.295-307
Main Authors: Sawchuk, Ronald J, Elmquist, William F
Format: Article
Language:English
Subjects:
Active transport
Animals
Biological Transport
Blood
Blood–brain barrier
Body fluids
Brain
Brain - metabolism
Brain microdialysis
Colchicine - pharmacokinetics
Controlled drug delivery
Drug efflux
Drug infusion
Drug products
Etoposide - pharmacokinetics
Humans
Microdialysis
Morphine - pharmacokinetics
Neurophysiology
P-Glycoprotein
Pharmacokinetics
Probenecid - pharmacology
Rhodamines - pharmacokinetics
Zidovudine - pharmacokinetics
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Summary: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.
ISSN:0169-409X
1872-8294
DOI:10.1016/S0169-409X(00)00104-6