The Extracellular Concentration of the Anti-epileptic Drug Valproate in the Rat Brain as Determined with Microdialysis and an Automated HPLC Procedure

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Abstract
The cellular and extracellular brain concentration of valproic acid in freely moving rats has been estimated after intravenous injection of sodium valproate. Some rats were provided with a stereotaxically implanted dialysis probe in the striatum and a cannula in the heart through which the drug was injected and which allowed regular removal of blood. In other rats tissue levels of valproic acid were determined 5 and 90 min after drug injection. Valproic acid was determined by an automated precolumn derivatization procedure followed by HPLC separation and fluorimetric detection. Extracellular concentration was proportional to the blood concentration at every time interval, indicating rapid exchange of the drug between the two compartments. About 50% of the striatal content of valproate was in the extracellular space. The experiments demonstrated the usefulness of microdialysis to estimate both the extracellular concentration and the average cellular drug levels, provided a sensitive analysis procedure is available.