METHODOLOGICAL CONSIDERATIONS OF INTRACEREBRAL MICRODIALYSIS IN PHARMACOKINETIC STUDIES ON DRUG TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER

Citation
Ecm. Delange et al., METHODOLOGICAL CONSIDERATIONS OF INTRACEREBRAL MICRODIALYSIS IN PHARMACOKINETIC STUDIES ON DRUG TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER, Brain research reviews, 25(1), 1997, pp. 27-49
Citations number
120
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0165-0173
Volume
25
Issue
1
Year of publication
1997
Pages
27 - 49
Database
ISI
SICI code
0165-0173(1997)25:1<27:MCOIMI>2.0.ZU;2-P
Abstract
For the study of the pharmacokinetics of drugs in the brain a number o f in vivo techniques is available, including autoradiography, imaging techniques, cerebrospinal fluid sampling and in vivo voltammetry, whic h all have their specific advantages and limitations. Intracerebral mi crodialysis is a relatively new in vivo technique. It permits monitori ng of local concentrations of drugs and metabolites at specific sites in the brain which makes it an attractive tool for pharmacokinetic res earch. In the use of this techique a number of factors should be consi dered. These include: type of probe, surgical trauma, post-surgery int erval, perfusion flow rate, as well as composition and temperature of the perfusion medium. In particular in studies on drug transport acros s the blood-brain barrier (BBB), effects of insertion of the probe on BBB functionality is important. It appears that BBB functionality is n ot significantly affected if surgical and experimental conditions are well-controlled The relationship between dialysate concentrations and those in the extracellular fluid of the periprobe tissue, the recovery of the drug, depends on periprobe processes governing the actual conc entration of the drug at that site. These include extracellular-microv ascular exchange, metabolism, and diffusion of the drug. Several metho ds have been proposed to determine recovery values. In particular the no net flux method and the extended no net flux method are useful in p ractice. Several microdialysis studies on BBB transport of drugs are p resented showing that intracerebral microdialysis is capable to assess local BBB transport profiles. Compared with other in vivo techniques, intracerebral microdialysis is the only (affordable) technique that o ffers the possibility to monitor-local BBB transport of drugs in unana esthetized animals, under physiological and pathological conditions. ( C) 1997 Elsevier Science B.V.