Therapeutic plasma levels of phenytoin, phenobarbital, and carbamazepine: Individual variation in relation to seizure frequency and type

The range and clinical features that influence the individual variation of the therapeutic plasma concentration of phenytoin, phenobarbital, and carbamazepine were studied in 84 epileptic patients on single-drug therapy. Complete cessation of seizures was observed at plasma concentrations of 17.9 (3 to 50) μg/ml phenytoin, 24.5 (3 to 43) μg/ml phenobarbital, and 6.5 (4.8 to 9.7) μg/ml carbamazepine. Fifty-one percent of the 53 patients receiving phenytoin were completely controlled at either below or above the 10 to 20 μg/ml range, suggesting that individual dosage adjustment is preferably based on clinical judgment rather than numerical limits of published therapeutic ranges. Fifty patients with therapeutic plasma concentrations of or above 15 μg/ml phenytoin, 25 μg/ml phenobarbital, or 6 μg/ml carbamazepine more often had partial epilepsies, complex partial seizures and, most markedly, a higher number of seizures in the first year of epilepsy and during the year prior to the present drug therapy, when compared with 34 patients with lower therapeutic plasma concentrations. The variation in therapeutic plasma concentration is primarily related to the type and to the severity of the individual epilepsy, as indicated by the seizure frequency at the onset of the epilepsy or prior to the treatment.