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Correlation between ethosuximide brain levels measured by high performance liquid chromatography and its
E Aguilar-Veiga1, G Sierra-Paredes, J Galán-Valiente
1Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago de Compostela, Spain.
Abstract:
The concentration-time curve of ethosuximide (ESM) in several brain zones of Wistar rats (cortex, midbrain, cerebellum) showed a clear difference from the time course of the drug levels in plasma after administration of 50 mg/kg injected by intraperitoneal route. The brain/plasma ratio in the cortex changes drastically from 2.04 +/- 0.14 (5 m after injection) to 0.14 +/- 0.01 (2 h after injection). Similar behaviour was observed in the brain/plasma ratio of midbrain and cerebellum. The antiepileptic potential of the ESM was closely related to the evolution of the drug time-course in the brain. Reversible opening of the blood-brain barrier modifies the cortex/plasma ratio from 0.14 +/- 0.01 to 0.79 +/- 0.11 (2h after ESM injection). Similar changes were observed in midbrain and cerebellum. The results suggest that the blood-brain barrier plays some part in the time-course of ESM in the brain, and emphasizes the role of brain levels measured by high performance liquid chromatography (HPLC) in clarifying the clinical profile of the drug.