Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.
Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.
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DOI：
10.1007/s00228-012-1373-8
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发表时间：
2013-03
影响因子：
2.9
通讯作者：
Kumagai, Yuji
中科院分区：
文献类型：
--
作者：
Tanaka, Jun;Kasai, Hidefumi;Shimizu, Kenji;Shimasaki, Shigeki;Kumagai, Yuji
关键词：
我们对健康、神经外科和癫痫受试者（包括儿科患者）静脉注射磷苯妥英钠后的苯妥英进行了群体药代动力学分析，并确定了达到治疗范围的最佳剂量和输注速率。我们使用了在日本进行的两项I期研究和一项III期研究的汇总数据。使用NONMEM软件进行群体药代动力学分析。使用最终模型获得的模拟结果确定最佳剂量和输注速率。苯妥英总血浆浓度的治疗范围为10-20 μg/mL。我们采用线性二房室模型，将磷苯妥英转换为苯妥英。苯妥英的药代动力学参数，如总清除率和中心和外周分布容积受体重的影响。剂量模拟如下。在成人患者中，达到治疗范围的苯妥英的最佳剂量和输注速率分别为22.5 mg/kg和3 mg/kg/min。在22.5 mg/kg（3 mg/kg/min）时，儿科患者中苯妥英的总血浆浓度在治疗范围内的持续时间短于成人患者。然而，许多儿科患者在30 mg/kg剂量给药后显示苯妥英浓度在毒性范围内。静脉注射磷苯妥英钠后苯妥英钠的药代动力学可用线性二室模型描述。以3 mg/kg/min的输注速率给予磷苯妥英钠22.5 mg/kg是达到所需血浆苯妥英浓度的最佳方案。
We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10–20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.
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影响因子：
2.5
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Frame, B;Beal, SL
通讯作者：
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