Distribution characteristics of ethosuximide in discrete areas of rat brain

The distribution properties of ethosuximide in four regions of the rat brain--cortex, midbrain, cerebellum, and pons-medulla--were investigated following chronic intraperitoneal administration of the drug (every 12 hr for 108 hr) at four dose levels (20, 40, 60, and 80 mg/kg). A gas-liquid chromatographic procedure was developed to quantitate ethosuximide levels in these tissues and plasma. The mean tissue/plasma ratios were 0.917, 0.942, 0.902, and 0.903 for cortex, midbrain, cerebellum, and pons-medulla, respectively. The distribution ratio for midbrain was significantly greater than that observed for cerebellum. For each brain region, the distribution ratio was independent of dose (20 to 80 mg/kg) and plasma concentration (8 to 135 microgram/ml).