Application of intracerebral microdialysis to study regional distribution kinetics of drugs in rat brain

British Journal of Pharmacology
E C de LangeD D Breimer

Abstract

1. The purpose of the present study was to determine whether intracerebral microdialysis can be used for the assessment of local differences in drug concentrations within the brain. 2. Two transversal microdialysis probes were implanted in parallel into the frontal cortex of male Wistar rats, and used as a local infusion and detection device respectively. Within one rat, three different concentrations of atenolol or acetaminophen were infused in randomized order. By means of the detection probe, concentration-time profiles of the drug in the brain were measured at interprobe distances between 1 and 2 mm. 3. Drug concentrations were found to be dependent on the drug as well as on the interprobe distance. It was found that the outflow concentration from the detection 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 kbp/Deff (transfer coefficient from brain to blood/effective diffusion coefficient in brain extracellular fluid), which was considerably larger for the more lipohilic drug, acetaminophen. In addition, in vivo recovery values for both drugs were determined. 4. The results show that intr...Continue Reading

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Citations

Sep 12, 2013·Cell and Tissue Research·Elmira Anderzhanova, Carsten T Wotjak
Mar 24, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Markus M ForsbergPekka T Männistö
Dec 8, 2000·Advanced Drug Delivery Reviews·E C de LangeD D Breimer
Jun 6, 2000·Advanced Drug Delivery Reviews· de Lange ECD D Breimer
Dec 5, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·E C de LangeW Couet
Nov 12, 2002·Respiratory Physiology & Neurobiology·Michelle L MessierEugene E Nattie
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Sep 10, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jasper StevensElizabeth C M de Lange
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May 17, 2019·Fluids and Barriers of the CNS·Esmée VendelElizabeth C M de Lange
May 28, 2019·Nature Reviews. Endocrinology·William A Banks

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