APPLICATION OF INTRACEREBRAL MICRODIALYSIS TO STUDY REGIONAL DISTRIBUTION KINETICS OF DRUGS IN RAT-BRAIN

Citation
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
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
0007-1188
Volume
116
Issue
5
Year of publication
1995
Pages
2538 - 2544
Database
ISI
SICI code
0007-1188(1995)116:5<2538:AOIMTS>2.0.ZU;2-F
Abstract
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.