Preliminary observations of serum carbamazepine concentration in epileptic patients

In preparation for a controlled study of the efficacy of carbamazepine in the treatment of epilepsy, a preliminary study of serum concentrations was done to determine (1) the relationship of serum concentration to dosage, (2) the rise and hourly variation of serum concentration and the rate of elimination from the blood, and (3) the optimal dosage for future studies in the involved population. Eight institutionalized white men with uncontrolled seizures and of similar age, weight and seizure classification and on similar medical regimens were selected for study. The first day, 200 mg of carbamazepine was added to the usual medication and thereafter increased by 200 mg daily, with two patients each remaining at constant dosages of 400, 800, 1200 or 1600 mg daily for 11 days. Blood was drawn daily four to four and one-half hours after the morning dose and at two, three, four and five hours after the morning dose on days 8 and 12. Serum levels of carbamazepine were determined by the Kupferberg method. The rise of average serum level concentration showed a significant Unear trend over the range of dosages studied. Average serum levels remained under 3 meg per milliliter with the 400 mg daily dosage, and ranged from 3 to 7 mcg per milliliter with the 800, 1200 and 1600 mg daily dosages. Carbamazepine was discontinued in one patient receiving 1600 mg daily for six days because of a unilateral sixth cranial nerve palsy and vomiting. Optimal dosage appeared to be 1200 mg. Elimination appears directly related to dosage or serum level, or both. Levels usually peaked three hours after the daily dosage, but much individual variation occurred.