Department of Pharmacy, Texas Children's Hospital, Houston, TX, USA.
Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Epilepsia. 2018 Jul;59(7):1327-1333. doi: 10.1111/epi.14447. Epub 2018 Jun 13.
Phenobarbital is frequently used in pediatric patients for treatment and prophylaxis of seizures. Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions.
A retrospective population pharmacokinetic analysis was designed for all pediatric patients <19 years of age initiated on phenobarbital at our institution from January 2011 to June 2017. Patients were included if they were initiated on intravenous or enteral phenobarbital for treatment or prophylaxis of seizures and had a serum phenobarbital concentration monitored while an inpatient. Data collection included the following: age, weight, height, gestational age, core body temperature, serum creatinine, blood urea nitrogen, aspartase aminotransferase, alanine aminotransferase, urine output over the prior 12 hours, phenobarbital doses and serum concentrations, and potential drug-drug interactions. Descriptive statistical methods were used to summarize the data. Pharmacokinetic analysis was performed with NONMEM and simulation was performed for doses of 10, 20, 30, and 40 mg kg dose , iv, followed by enteral doses of 3, 4, 5, and 6 mg kg d .
A total of 355 patients (50.3% male, median gestational age 39 weeks (interquartile range [IQR] 35, 40), median age 0.28 years (IQR 0.06, 0.82). Median phenobarbital dose was enteral = 2.6 (IQR 1.9, 3.9) mg kg dose ; intravenous = 2.6 (IQR 2.2, 4.9) mg kg dose ) and mean serum concentration was 41.1 ± 23.9 mg/L at median 6.5 (IQR 2.9, 11.1) hours after a dose. A one-compartment proportional error model best fit the data where clearance and volume of distribution were allometrically scaled using fat-free mass. Significant covariates included serum creatinine, postmenstrual age, and drug-drug interactions on clearance, and age in years on volume of distribution.
Phenobarbital dosing of 30 mg kg dose ,iv, followed by 4 mg kg d had the highest probability of attaining a therapeutic concentration at 7 days. Postmenstrual age and drug-drug interactions should be incorporated into dosing decisions.
苯巴比妥常用于儿科患者的癫痫治疗和预防。该患者群体的药代动力学数据缺乏，将有助于指导剂量决策。
本研究设计了一项回顾性群体药代动力学分析，纳入了 2011 年 1 月至 2017 年 6 月期间在我院接受苯巴比妥治疗或预防癫痫发作的所有年龄<19 岁的儿科患者。如果患者接受静脉或肠内苯巴比妥治疗且住院期间监测了血清苯巴比妥浓度，则将其纳入研究。数据收集包括：年龄、体重、身高、胎龄、核心体温、血清肌酐、血尿素氮、前 12 小时尿量、苯巴比妥剂量和血清浓度，以及潜在的药物相互作用。采用描述性统计方法对数据进行总结。NONMEM 进行药代动力学分析，模拟剂量为 10、20、30 和 40mg/kg，iv 后给予肠内剂量 3、4、5 和 6mg/kg。
共纳入 355 例患者（50.3%为男性，中位胎龄 39 周（四分位距 [IQR] 35，40），中位年龄 0.28 岁（IQR 0.06，0.82）。肠内苯巴比妥中位剂量为 2.6（IQR 1.9，3.9）mg/kg；静脉内苯巴比妥中位剂量为 2.6（IQR 2.2，4.9）mg/kg），中位血清浓度为 41.1±23.9mg/L，在中位 6.5（IQR 2.9，11.1）小时后给药。数据最符合一室比例误差模型，清除率和分布容积按去脂体重进行体表面积标化。有意义的协变量包括清除率方面的血清肌酐、月经后年龄和药物相互作用，以及分布容积方面的年龄。
30mg/kg，iv，继以 4mg/kg，d 的苯巴比妥剂量方案，在 7 天内达到治疗浓度的概率最高。月经后年龄和药物相互作用应纳入剂量决策。
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