[Population pharmacokinetics of phenytoin in pediatric patients].

ABSTRACT

OBJECTIVE: To study population pharmacokinetics of phenytoin in pediatric patients by using sparse data. METHODS: We used routinely collected therapeutic drug monitoring data, derived from the steady state serum concentrations of phenytoin in 42 pediatric outpatients with epilepsy. Depending on whether the patients were administered with phenytoin alone or coadministered with phenobabital or clonazepam, the subjects were divided into two groups phenytoin group and coadministration group. The population parameter and individual parameter of phenytoin in children were estimated using Monte Carlo method. RESULTS: The children's phenytoin population pharmacokinetic parameters Vm and Km were 9.8 mg.kg(-1).d(-1) and 2.73 mg/L in phenytoin group; and 9.2 mg.kg(-1).d(-1) and 3.24 mg/L in coadministration group. There were good relationship between predicted and determined concentrations with correlation coefficient of 0.999 and 0.984, respectively. CONCLUSION: The coadministration of phenobarbital or clonazepam obviously affected the pharmacokinetics of phenytoin. The population pharmacokinetics of phenytoin in children may provide a usefull index for individualization of dosage regimen.