Phenytoin and phenobarbitone plasma level-dose relationships in Chinese epileptic children in Singapore

In a study of 30 Chinese epileptic children, 43% had poor seizure control. The average daily dose of phenytoin was 6.1 +/- 0.53 mg/kg, and the mean plasma level was 4.2 +/- 0.63 microgram/ml, as determined by the enzyme immunoassay (EMIT) method. The phenytoin plasma level (microgram/ml) versus daily dose (mg/kg) ratios in 73% of these patients were below 1. The average daily dose of phenobarbitone was 5.1 +/- 0.36 mg/kg, and the mean plasma level was 24.8 +/- 1.7 microgram/ml -- also estimated by EMIT. Only one patient showed adverse effects. Poor seizure control in patients was chiefly due to subtherapeutic concentrations of phenytoin, which cannot be attributed to poor patient compliance. The presence of phenobarbitone might have accelerated phenytoin metabolism, or the drug could have been lost through sweating. The pharmacokinetics of phenytoin in these Chinese children may be genetically different and might have caused the subtherapeutic phenytoin levels.