Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and serum concentrations of antiepileptic drugs measured intraoperatively in patients with intractable epilepsy

Epilepsia
Bernhard RambeckWolfgang Löscher

Abstract

The mechanisms of drug resistance in epilepsy are only incompletely understood. According to a current concept, overexpression of drug efflux transporters at the blood-brain barrier may reduce levels of antiepileptic drugs (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux transporters such as P-glycoprotein has been found in brain tissue surgically resected from patients with medically intractable epilepsy, but it is not known whether this leads to decreased extracellular (interstitial) AED concentrations in affected brain regions. This prompted us to measure concentrations of AEDs in the extracellular space of human neocortical tissue by using intraoperative microdialysis (IOMD) in those parts of the brain that had to be removed for therapeutic reasons. For comparison, AED levels were determined in brain tissue, subarachnoid CSF, and serum. Concentrations of carbamazepine (CBZ), 10-hydroxy-carbazepine (10-OH-CZ, metabolite of oxcarbazepine), lamotrigine (LTG), levetiracetam (LEV), topiramate, or phenytoin were determined by using one to four catheters during IOMD in the medial temporal gyrus. Furthermore, to calculate the individual recovery of every catheter, an in vitro microdialysis was performed wit...Continue Reading

References

Jul 1, 1994·Epilepsy Research·R D ScheyerR H Mattson
Oct 7, 1998·Epilepsy Research·J Engel
Apr 21, 1999·Epilepsy Research·G Regesta, P Tanganelli
Feb 5, 2000·The New England Journal of Medicine·P Kwan, M J Brodie
May 12, 2000·British Journal of Pharmacology·M C WalkerP N Patsalos
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Wolfgang Löscher, Heidrun Potschka
Sep 24, 2004·Advanced Drug Delivery Reviews·Danny D ShenKimberly K Adkison
Nov 3, 2004·Seizure : the Journal of the British Epilepsy Association·Xiaolan WangPhilip N Patsalos
Jan 26, 2005·Annals of Neurology·Rudie KortekaasN Harry Hendrikse
Jun 11, 2005·Epilepsia·Dieter Schmidt, Wolfgang Löscher
Jun 18, 2005·Clinical Pharmacology and Therapeutics·Lucy SasongkoJashvant D Unadkat
Jul 14, 2005·Progress in Neurobiology·Wolfgang Löscher, Heidrun Potschka
Jul 19, 2005·Nature Reviews. Neuroscience·Wolfgang Löscher, Heidrun Potschka

❮ Previous
Next ❯

Citations

Jun 6, 2007·Nature Clinical Practice. Neurology·Sanjay Sisodiya
Feb 24, 2007·Epilepsia·Wolfgang Löscher
Apr 10, 2008·Epilepsia·Charles M EpsteinJoshua Andrew Ehrenberg
Aug 22, 2009·Epilepsia·Margherita D'AntuonoMassimo Avoli
Apr 16, 2010·Science Translational Medicine·T Janowitz, D K Menon
Jul 1, 2008·Therapeutic Advances in Neurological Disorders·Rainer SurgesMatthew C Walker
Jan 25, 2013·International Journal of Molecular Sciences·Noemi Cardenas-RodriguezElvia Coballase-Urrutia
Jul 16, 2010·Journal of Endocrinological Investigation·J A Llompart-PouJ M Raurich
Feb 13, 2013·Journal of Pharmacokinetics and Pharmacodynamics·Elizabeth C M de Lange
Jan 5, 2013·Therapeutic Drug Monitoring·Philip N Patsalos, Dave J Berry
Mar 14, 2007·Current Opinion in Neurology·Ettore Beghi
May 23, 2015·The International Journal of Neuroscience·Guang-Xin WangYan-Hui Ma
Jan 1, 2009·Expert Opinion on Drug Discovery·Doru Georg Margineanu, Henrik Klitgaard
Jul 31, 2007·Expert Opinion on Pharmacotherapy·Sarah K Tate, Sanjay M Sisodiya
Jul 21, 2009·Expert Opinion on Drug Metabolism & Toxicology·Ralph ClinckersOscar Della Pasqua
Nov 4, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S G SummerfieldA D Ruffo
Oct 5, 2013·Epilepsy & Behavior : E&B·Doru Georg Margineanu
Mar 20, 2012·Neurobiology of Disease·Chaitali GhoshDamir Janigro
Dec 27, 2011·Advanced Drug Delivery Reviews·Chunbo ZhangLarry Baum
Sep 18, 2007·Neuroscience Letters·Zhi-qin XiXue-feng Wang
Mar 13, 2008·Journal of Neuroscience Research·Aiden HaghikiaPedro M Faustmann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Blood-Brain Barrier Transport in Neurodegeneration

The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.