Correlation between ethosuximide brain levels measured by high performance liquid chromatography and its antiepileptic potential.
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.
Aguilar-Veiga
E
E
Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago de Compostela, Spain.
Sierra-Paredes
G
G
Galán-Valiente
J
J
Soto-Otero
R
R
Méndez-Alvarez
E
E
Sierra-Marcuño
G
G
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D005013:Ethosuximide / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D014018:Tissue Distribution
D000927:Anticonvulsants; D005013:Ethosuximide; D010433:Pentylenetetrazole