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The efficacy and bioavailability, and tolerance to carbamazepinee when administered with phenobarbital or phenytoin or with both drugs were evaluated in a prospective, double-blind study of patients whose seizures were not completely controlled by currently available antiepileptic drugs in usually therapeutic dosages as determined by serum levels. During each of four 21-day treatment periods, one fourth of the patients received daily doses of: (1) carbamazepine (1,200 mg) and phenytoin (300 mg); (2) carbamazepine (1,200 mg) and phenobarbital (300 mg); (3) phenytoin (300 mg) and phenobarbital (300 mg); or (4) carbamazepine (1,200 mg), with phenytoin (300 mg) and phenobarbital (300 mg). The treatment periods were separated by 2 wk of each patient's usual prestudy medication. Treatment with all three drugs was the most efficacious for seizure control. Serum carbamazepine concentration was significantly decreased when the drug was administered with either phenytoin or phenobarbital or both.

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