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Further observations on carbamazepine plasma levels in epileptic patients

Relationships with therapeutic and side effects

From the Clinic of Nervous and Mental Diseases, University Medical School, Turin, and the Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.

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/ug per milliliter. A remarkable drop in seizure frequency was attained within 2 to 3 weeks of monitoring, with carbamazepine plasma 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 carbamazepine-10,11-epoxide 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.

Dr. Morselli's present address is Clinic of Nervous and Mental Diseases, Medical School, University of Sassari, Paris, France.

This study was partially supported by a grant from Ciba-Geigy, Milan, Italy.

Received for publication December 1, 1975.

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