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  • Title: Methodological considerations of intracerebral microdialysis in pharmacokinetic studies on drug transport across the blood-brain barrier.
    Author: de Lange EC, Danhof M, de Boer AG, Breimer DD.
    Journal: Brain Res Brain Res Rev; 1997 Sep 30; 25(1):27-49. PubMed ID: 9370049.
    Abstract:
    For the study of the pharmacokinetics of drugs in the brain a number of in vivo techniques is available, including autoradiography, imaging techniques, cerebrospinal fluid sampling and in vivo voltammetry, which all have their specific advantages and limitations. Intracerebral microdialysis is a relatively new in vivo technique. It permits monitoring of local concentrations of drugs and metabolites at specific sites in the brain which makes it an attractive tool for pharmacokinetic research. In the use of this technique a number of factors should be considered. These include: type of probe, surgical trauma, post-surgery interval, perfusion flow rate, as well as composition and temperature of the perfusion medium. In particular in studies on drug transport across the blood-brain barrier (BBB), effects of insertion of the probe on BBB functionality is important. It appears that BBB functionality is not 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 concentration of the drug at that site. These include extracellular-microvascular exchange, metabolism, and diffusion of the drug. Several methods have been proposed to determine recovery values. In particular the no net flux method and the extended no net flux method are useful in practice. Several microdialysis studies on BBB transport of drugs are presented 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 offers the possibility to monitor local BBB transport of drugs in unanaesthetized animals, under physiological and pathological conditions.
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