Massie John, Cranswick Noel
Department of Respiratory Medicine, University of Melbourne, Melbourne, Victoria, Australia.
J Paediatr Child Health. 2006 Oct;42(10):601-5. doi: 10.1111/j.1440-1754.2006.00944.x.
Once-daily tobramycin in patients with cystic fibrosis (CF) is a more convenient dosing regimen than thrice daily dosing. There are limited data on the pharmacokinetic (PK) profile for once-daily tobramycin in patients with CF. The aim of this study was to define the PK parameters for once-daily tobramycin in children with CF and develop an algorithm for therapeutic drug monitoring dosing.
CF patients admitted to hospital were commenced on once-daily intravenous tobramycin (12 mg/kg/day) and ticarcillin/clavulinic acid. Serum tobramycin levels were taken at 30 min, 2-4 h and 12 h post dose. Data points for the PK model included: age, sex, weight, tobramycin dose, time of tobramycin doses and levels, tobramycin levels. WinNonMix was used to obtain the PK parameters.
Forty-four children with 86 admissions who were aged 9 months-20 years were included. A one-compartment intravenous infusion model with first order elimination kinetics produced the best model. Population parameters were: volume of distribution (V(d)) = 0.267 L/kg (95% confidence interval (CL) 0.260-0.272), clearance (CL) 0.103 L/kg/h (95% CI 0.098-0.107) and half-life (t(1/2)) 1.82 (95% CI 1.77-1.88) h. Once the population model was established post hoc analysis was used to calculate individual subject predictions. Plots of individual prediction curves agreed well with observed values.
This study has established an algorithm for routine monitoring of once-daily tobramycin in children with CF. Satisfactory serum levels of tobramycin were obtained with a dose of 12 mg/kg/day and a regimen algorithm that uses only one measurement to monitor the plasma concentration is suggested.
对于囊性纤维化（CF）患者，每日一次使用妥布霉素的给药方案比每日三次给药更为便捷。关于CF患者每日一次使用妥布霉素的药代动力学（PK）特征的数据有限。本研究的目的是确定CF患儿每日一次使用妥布霉素的PK参数，并开发一种治疗药物监测给药算法。
入院的CF患者开始每日一次静脉注射妥布霉素（12mg/kg/天）和替卡西林/克拉维酸。在给药后30分钟、2 - 4小时和12小时采集血清妥布霉素水平。PK模型的数据点包括：年龄、性别、体重、妥布霉素剂量、妥布霉素给药时间和水平、妥布霉素水平。使用WinNonMix获得PK参数。
纳入了44名年龄在9个月至20岁之间、有86次入院记录的儿童。具有一级消除动力学的单室静脉输注模型产生了最佳模型。群体参数为：分布容积（V(d)）= 0.267L/kg（95%置信区间（CL）0.260 - 0.272），清除率（CL）0.103L/kg/小时（95%CI 0.098 - 0.107），半衰期（t(1/2)）1.82（95%CI 1.77 - 1.88）小时。一旦建立群体模型，就使用事后分析来计算个体受试者预测值。个体预测曲线与观察值吻合良好。
本研究建立了一种用于CF患儿每日一次妥布霉素常规监测的算法。使用12mg/kg/天的剂量可获得满意的妥布霉素血清水平，并建议采用仅使用一次测量来监测血浆浓度的给药方案算法。
