Distribution of Plasma Phenobarbital, Diphenylhydantoin and Primidone Levels in Epileptic Patients

SUMMARY Plasma DPH, PB and primidone level were determined in 142 patients with epilepsy by using enzyme immunoassay measurement. 1 . The average plasma concentrations of DPH in patients that received DPH (101 cases), in the seizure controlled group (22) and the uncontrolled group were 2.76±0.33 μg/ml, 2.23±0.57 μg/ml and 1.96±0.59 μg/ml, respectively. 2 . As to the distribution of the plasma DPH level, it widely ranged from a minimum value of 0 μg/ml to a maximum value of 27.5 μg/ml and the median value was 1.5 μg/ml. 3 . There were only two patients with a plasma DPH level that remained within the range of its therapeutic concentration which had been reported in Europe and America (10–20 μg/ml). Therefore, it is considered that the therapzutic concentration in Japan is markedly lower. 4 . The plasma PB levels in the total patients and in the seizure controlled group were 24.75±1.49 μg/ml and 25.19±3.16 μg/ml, respectively. As the plasma concentration in the seizure uncontrolled group was 21.96±3.70μglml, no significant difference was observed between the two groups—the seizure controlled group and the uncontrolled group. 5 . Most of the patients with higher plasma level were treated with the combination therapy of primidone and methylphenobarbital. Therefore, the plasma PB level does not become in excess when the two drugs are combined with P.B 6 . The plasma primidone level in all patients tested was 7.03±0.66 μg/ml. The plasma levels in the seizure controlled group and the uncontrolled group were 5.80μ1.03 μg/ml and 8.25±1.57 μg/ml, respectively, with no significant difference between the two groups. 7 . In the primidone-administered group, the ratio of the plasma primidone level to the plasma PB level was 10.68. 8 . The factors which may influence plasma DPH, PB and primidone levels were discussed.