1Serum and CSF samples of patients receiving chronic carbamazepine treatment were analysed. 2 Daily fluctuations in serum levels of carbamazepine and carbamazepine-10, 11-epoxide did not appear to be related to the dosage schedule, but some patients tended to have lower fluctuations when the carbamazepine was given more frequently. 3 The epoxide/carbamazepine serum ratios varied greatly from patient to patient, and also fluctuated during the day for the same patient. 4 Carbamazepine and carbamazepine-10,11-epoxide were present in CSF in concentrations ranging from 19 to 34% and 26 to 71 % of the serum concentrations, respectively.5 There was a significant relationship between the free fraction of both drugs evaluated in vivo and the CSF/serum ratios. 6 The need for a careful evaluation of the possible clinical effect of the epoxide is stressed.

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Plasma levels of carbamazepine, phenytoin and phenobarbital were monitored weekly over a period of 9 weeks in 20 epileptic patients unresponsive to treatment. No attempts were made to modify phenytoin and/or phenobarbital plasma levels; emphasis was on achieving carbamazepine plasma levels of 4 to 10 mug per milliliter. A remarkable drop in seizure frequency was attained within 2 to 3 weeks of monitoring, with carbamazepine plasma and concentrations within the desired range. Children disposed of the drug faster than adults. No effects of phenytoin and phenobarbital on carbamazepine plasma levels could be observed, while phenobarbital on carbamazepine plasma levels fluctuated remarkably without any relationship to carbamazepine levels. Transient leukopenia was present in most of the patients, while a significant reversible drop in red blood cells was observed in eight patients. The data reported confirm that with a careful monitoring of drug plasma levels, carbamazepine may exert a definite passive effect on seizure frequency in epileptic patients poorly responsive to therapy.

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