使用贝叶斯估计法对儿童进行万古霉素监测。
Vancomycin monitoring in children using bayesian estimation.
作者信息
Le Jennifer, Ngu Becky, Bradley John S, Murray William, Nguyen Austin, Nguyen Lyn, Romanowski Gale L, Vo Tiana, Capparelli Edmund V
机构信息
*Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla; †Miller Children's Hospital, Long Beach; and ‡Rady Children's Hospital, San Diego, CA.
出版信息
Ther Drug Monit. 2014 Aug;36(4):510-8. doi: 10.1097/FTD.0000000000000039.
BACKGROUND
Optimal monitoring of vancomycin in children needs evaluation using the exposure target with area under the curve (AUC) of the serum concentrations versus time over 24 hours. Our study objectives were to: (1) compare the accuracy and precision of vancomycin AUC estimations using 2 sampling strategies-1 serum concentration sample (1S, near trough) versus 2 samples (2S, near peak and trough) against the rich sample (RS) method; and (2) determine the performance of these strategies in predicting future AUC against an internal validation sample (VS).
METHODS
This was a retrospective cohort study using population-based pharmacokinetic modeling with Bayesian post hoc individual estimations in nonlinear mixed effects modeling (version 7.2). Pediatric subjects 3 months-21 years of age who received vancomycin ≥48 hours and had more than 3 drug samples within the first ≤96 hours of therapy were enrolled. Outcome measures were the accuracy, precision, and internal predictive performance of AUC estimations using 2 monitoring strategies (ie, 1S versus 2S) against the RS (which was derived from modeling all serum vancomycin concentrations obtained anytime during therapy) and VS (from serum concentrations obtained after 96 hours of therapy).
RESULTS
Analysis included 138 subjects with 712 vancomycin serum concentrations. Median age was 6.1 (interquartile range, 2.2-12.2) years, weight 22 (13-38) kg, and baseline serum creatinine 0.37 (0.30-0.50) mg/dL. Both accuracy and precision were improved with the 2S, compared with 1S, for AUC estimations (-2.0% versus -7.6% and 10.3% versus 12.8%, respectively) against the RS. Improved accuracy and precision were also observed for 2S when evaluated against VS in predicting future AUC.
CONCLUSIONS
Compared with 1S, the 2S sampling strategy for vancomycin monitoring improved accuracy and precision in estimating and predicting future AUC. Evaluating 2 drug concentrations in children may be prudent to ensure adequate drug exposure.
背景
儿童万古霉素的最佳监测需要使用血清浓度-时间曲线下面积（AUC）作为暴露目标进行评估，该曲线反映24小时内血清浓度随时间的变化。我们的研究目的是：（1）比较使用两种采样策略（1个血清浓度样本（1S，接近谷浓度）与2个样本（2S，接近峰浓度和谷浓度））估算万古霉素AUC的准确性和精密度，并与丰富样本（RS）法进行对比；（2）针对内部验证样本（VS），确定这些策略在预测未来AUC方面的性能。
方法
这是一项回顾性队列研究，采用基于人群的药代动力学建模以及非线性混合效应建模（版本7.2）中的贝叶斯事后个体估计。纳入3个月至21岁接受万古霉素治疗≥48小时且在治疗的前≤96小时内有超过3个药物样本的儿科受试者。结局指标是使用两种监测策略（即1S与2S）相对于RS（通过对治疗期间任何时间获得的所有血清万古霉素浓度进行建模得出）和VS（治疗96小时后获得的血清浓度）估算AUC的准确性、精密度和内部预测性能。
结果
分析包括138名受试者，共712个万古霉素血清浓度。中位年龄为6.1岁（四分位间距，2.2 - 12.2岁），体重22 kg（13 - 38 kg），基线血清肌酐0.37 mg/dL（0.30 - 0.50 mg/dL）。与1S相比，2S在估算AUC时相对于RS的准确性和精密度均有所提高（分别为 - 2.0%对 - 7.6%以及10.3%对12.8%）。在针对VS预测未来AUC时，2S的准确性和精密度也有所提高。
结论
与1S相比，用于万古霉素监测的2S采样策略在估算和预测未来AUC方面提高了准确性和精密度。评估儿童的两种药物浓度可能有助于确保足够的药物暴露。
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