Ecm. Delange et al., APPLICATION OF INTRACEREBRAL MICRODIALYSIS TO STUDY REGIONAL DISTRIBUTION KINETICS OF DRUGS IN RAT-BRAIN, British Journal of Pharmacology, 116(5), 1995, pp. 2538-2544
1 The purpose of the present study was to determine whether intracereb
ral microdialysis can be used for the assessment of local differences
in drug concentrations within the brain. 2 Two transversal microdialys
is probes were implanted in parallel into the frontal cortex of male W
istar rats, and used as a local infusion and detection device respecti
vely. Within one rat, three different concentrations of atenolol or ac
etaminophen were infused in randomized order. By means of the detectio
n probe, concentration-time profiles of the drug in the brain were mea
sured at interprobe distances between 1 and 2 mm. 3 Drug concentration
s were found to be dependent on the drug as well as on the interprobe
distance. It was found that the outflow concentration from the detecti
on probe decreased with increasing lateral spacing between the probes
and this decay was much steeper for acetaminophen than for atenolol. A
model was developed which allows estimation of k(bp)/D-eff (transfer
coefficient from brain to blood/effective diffusion coefficient in bra
in extracellular fluid), which was considerably larger for the more li
pohilic drug, acetaminophen. In addition, in vivo recovery values for
both drugs were determined. 4 The results show that intracerebral micr
odialysis is able to detect local differences in drug concentrations f
ollowing infusion into the brain. Furthermore, the potential use of in
tracerebral microdialysis to obtain pharmacokinetic parameters of drug
distribution in brain by means of monitoring local concentrations of
drugs in time is demonstrated.