Vancomycin monitoring in children using bayesian estimation.
Vancomycin monitoring in children using bayesian estimation.
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DOI：
10.1097/ftd.0000000000000039
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发表时间：
2014-08
影响因子：
2.5
通讯作者：
Capparelli EV
中科院分区：
文献类型：
--
作者：
Le J;Ngu B;Bradley JS;Murray W;Nguyen A;Nguyen L;Romanowski GL;Vo T;Capparelli EV
儿童万古霉素的最佳监测需要使用血清浓度曲线下面积与24小时时间（AUC）的暴露目标进行评估。我们的研究目的是：(1)比较两种采样策略——一种血清浓度样本（1S，近波谷）与两种样本（2S，近波峰和波谷）与富样本（RS）法估算万古霉素AUC的准确性和精密度；(2)根据内部验证样本（VS）确定这些策略在预测未来AUC方面的性能。这是一项回顾性队列研究，在NONMEM 7.2中使用基于人群的药代动力学模型和贝叶斯事后个体估计。纳入3个月至21岁的儿童受试者，他们接受万古霉素治疗≥48小时，并且在治疗的第一个≤96小时内有≥3个药物样本。结果测量是使用两种监测策略（即1S vs 2S）对RS（通过模拟治疗期间任何时间获得的所有血清万古霉素浓度）和vs（治疗96小时后获得的血清浓度）进行AUC估计的准确性、精密度和内部预测性能。分析纳入138名受试者，血清万古霉素浓度为712。中位年龄为6.1岁（四分位数间距[IQR] 2.2-12.2）岁，体重为22 (13-38)kg，基线血清肌酐为0.37 (0.30-0.50)mg/dL。与1S相比，2S对AUC估计的准确度和精密度都比RS有所提高（分别为-2.0%对- 7.6%和10.3%对12.8%）。在预测未来AUC时，与vs相比，2S的准确度和精密度也有所提高。与1S相比，用于万古霉素监测的2S采样策略提高了估计和预测未来AUC的准确性和精密度。评估两种药物在儿童中的浓度可能是谨慎的，以确保充分的药物暴露。
Optimal monitoring of vancomycin in children needs evaluation using the exposure target with area-under-the-curve of the serum concentrations vs. time over 24 hours (AUC). Our study objectives were to: (1) compare the accuracy and precision of vancomycin AUC estimations using two sampling strategies – one serum concentration sample (1S, near trough) versus two 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). This was an retrospective cohort study using population-based pharmacokinetic modeling with Bayesian post-hoc individual estimations in NONMEM 7.2. Pediatric subjects 3 months to 21 years of age who received vancomycin ≥ 48 hours and had ≥ 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 two monitoring strategies (i.e., 1S vs 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). Analysis included 138 subjects with 712 vancomycin serum concentrations. Median age was 6.1 (interquartile range [IQR] 2.2-12.2) yr, 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 to 1S, for AUC estimations (-2.0% vs -7.6 % and 10.3% vs 12.8%, respectively) against the RS. Improved accuracy and precision were also observed for 2S when evaluated against VS in predicting future AUC. Compared to 1S, the 2S sampling strategy for vancomycin monitoring improved accuracy and precision in estimating and predicting future AUC. Evaluating two drug concentrations in children may be prudent to ensure adequate drug exposure.