Brain distribution and efficacy of carbamazepine in kainic acid induced seizure in rats

To investigate the relationships between carbamazepine (CBZ) concentrations in serum and the brain, and the anticonvulsive efficacy in kainic acid (KA ) induced seizures in rats, adult Wistar rats (n = 25) were intraperitoneal ly given 40 mg/kg CBZ. followed by 15 mg/kg KA (n = 20) or saline (control. n = 5). At 90 min after the injection, CBZ concentrations in 5 rats withou t seizures (CBZ effective group), 5 mts with seizures (CBZ no-effective gro up) and five control rats were measured. Serum and brain tissues from six a reas (cortex, brain stem, cerebellum, thalamus, hippocampus and striatum) w ere used for CBZ assay. CBZ wits measured using a EMIT immunoassay kit. In blood, CBZ was higher in rats treated with CBZ + KA than in a control group (CBZ + saline), in the brain, the effective group demonstrated significant ly high CBZ concentration in the hippocampus. KA appeared to raise serum CB Z level when it was given in combination with CBZ. This was probably caused by the accelerated absorption of CBZ from local site us the results of an increased metabolic rate and the more demands for blood supply after KA tre atment. The positive correlation between efficacy of CBZ and the concentrat ion in the hippocampus suggests that CBZ levels in the hippocampus is close ly correlated with the efficacy of CBZ against KA induced seizures. (C) 200 0 Elsevier Science B.V. All rights reserved.