儿童苯妥因群体药动学研究

目的 :研究儿童苯妥因的群体药动学。方法 :收集 4 2例门诊患儿的常规治疗药物监测数据 ,应用自编程序 Monte Carlo法提取儿童苯妥因群体药动学参数和个体药动学参数。结果 :儿童苯妥因群体药动学参数 Vm和Km分别为单独用药组 9.8mg· kg-1· d-1和 2 .73mg/ L,合并用药组 9.2 mg·kg-1·d-1和 3.2 4 mg/ L;预测血药浓度与实测浓度显著相关 (r分别为 0 .999和 0 .984 ,P<0 .0 1)。结论 :合用苯巴比妥或氯硝安定对苯妥因的药动学有显著影响。本研究为儿童苯妥因给药方案个体化提供有价值的依据。

Population pharmacokinetics of phenytoin in pediatric patients

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.