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 intraperitoneally 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 without seizures (CBZ effective group), 5 rats with seizures (CBZ no-effective group) and five control rats were measured. Serum and brain tissues from six areas (cortex, brain stem, cerebellum, thalamus, hippocampus and striatum) were used for CBZ assay. CBZ was 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 significantly high CBZ concentration in the hippocampus. KA appeared to raise serum CBZ level when it was given in combination with CBZ. This was probably caused by the accelerated absorption of CBZ from local site as the results of an increased metabolic rate and the more demands for blood supply after KA treatment. The positive correlation between efficacy of CBZ and the concentration in the hippocampus suggests that CBZ levels in the hippocampus is closely correlated with the efficacy of CBZ against KA induced seizures.
Wang
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Pediatric Neurology, First Teaching Hospital, Beijing Medical University, Beijing, People's Republic of China. txywlshu@public.bta.net.cn
Zuo
C H
CH
Zhao
D Y
DY
Wu
X R
XR
D000818:Animals; D000927:Anticonvulsants / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D002220:Carbamazepine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D002220:Carbamazepine; D007608:Kainic Acid