Correlation between ethosuximide brain levels measured by high performance liquid chromatography and its antiepileptic potential
Aguilar-Veiga, E.; Sierra-Paredes, G.; Galán-Valiente, J.; Soto-Otero, R.; Méndez-Alvarez, E.; Sierra-Marcuño, G.
Research Communications in Chemical Pathology and Pharmacology 71(3): 351-364
1991
ISSN/ISBN: 0034-5164 PMID: 2047576 Document Number: 373123
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 (2 h 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.