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
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.