Brain distribution of carbamazepine and phenobarbital given in combination in experimental epilepsy

This study describes the brain distribution of carbamazepine (CBZ) and phenobarbital (PB) given intraperitoneally in combination to cats rendered epileptic by parenteral penicillin and by penicillin topically applied on neocortex. A control group of normal cats was also evaluated pharmacokinetically. Levels of both drugs were extremely low in brains of controls (CBZ 0.8 +/- 0.02 micrograms/g; PB 1.49 +/- 0.7 micrograms/g of fresh tissue), but higher levels were found in brains of epileptic cats with CBZ showing the greater increase (peak concentrations five- to sixfold higher than the corresponding CSF free fraction vs. three- to fourfold higher for PB). This might have been partially due to the ability of CBZ to prevent the metabolic alterations associated with severe convulsions, and hence the binding impairment. As this event had no effect of potentiation on CBZ anticonvulsant activity, the present data confirm previous reports indicating that there is no experimental evidence that two drugs are better than one in controlling epilepsy.