Kevin J Downes, Anna Sharova, Judith Malone, Audrey R Odom John, Athena F Zuppa, Michael N Neely
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During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software. The model was embedded in InsightRx NOVA (InsightRx, Inc.) for individual Bayesian estimation of AUC using the optimal sample versus all available samples (optimally timed sample + clinical samples).</p><p><strong>Results: </strong>Eighteen children were included. The optimal sampling time to inform Bayesian estimation of vancomycin AUC was highly variable, with trough samples being optimally informative in 32% of children. Optimal samples were collected by clinical nurses within 15 minutes of the goal time in 14 of 18 participants (78%). Compared with all samples, Bayesian AUC estimation with optimal samples had a mean bias of 0.4% (±5.9%) and mean imprecision of 4.6% (±3.6%). Bias of optimal sampling was <10% for 17 of the 18 participants (94%). When estimating AUC using only a peak sample (≤2 hours after dose) or only a trough (≤30 minutes before next dose), bias was <10% for 78% and 86% of participants, respectively.</p><p><strong>Conclusions: </strong>Optimal sampling supports accurate Bayesian estimation of vancomycin AUC from a single plasma sample in critically ill children.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children.\",\"authors\":\"Kevin J Downes, Anna Sharova, Judith Malone, Audrey R Odom John, Athena F Zuppa, Michael N Neely\",\"doi\":\"10.1097/FTD.0000000000001293\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.</p><p><strong>Methods: </strong>The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. 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引用次数: 0
摘要
背景:推荐使用曲线下面积(AUC)导向的万古霉素治疗;然而,由于需要多个样本和缺乏信息模型,危重儿童的AUC估计是困难的。方法:作者前瞻性地纳入了因疑似感染而接受静脉注射万古霉素(IV)治疗的危重儿童,并评估了贝叶斯估计单一最佳时间样本AUC的准确性。在给药间隔期间,当进行临床治疗药物监测时,收集最佳时间样本,并使用已建立的群体药代动力学模型和Pmetrics(非参数群体药代动力学建模软件)的多模型优化函数确定每个受试者的最佳时间样本。该模型嵌入InsightRx NOVA (InsightRx, Inc.)中,使用最佳样本与所有可用样本(最佳时间样本+临床样本)进行单个贝叶斯AUC估计。结果:纳入18例患儿。对万古霉素AUC进行贝叶斯估计的最佳采样时间是高度可变的,在32%的儿童中,通过样本获得最佳信息。临床护士在目标时间15分钟内收集到的最佳样本在18名参与者中有14名(78%)。与所有样本相比,最优样本贝叶斯AUC估计的平均偏差为0.4%(±5.9%),平均不精度为4.6%(±3.6%)。结论:最优抽样支持危重患儿单份血浆样本万古霉素AUC的准确贝叶斯估计。
Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children.
Background: Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.
Methods: The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software. The model was embedded in InsightRx NOVA (InsightRx, Inc.) for individual Bayesian estimation of AUC using the optimal sample versus all available samples (optimally timed sample + clinical samples).
Results: Eighteen children were included. The optimal sampling time to inform Bayesian estimation of vancomycin AUC was highly variable, with trough samples being optimally informative in 32% of children. Optimal samples were collected by clinical nurses within 15 minutes of the goal time in 14 of 18 participants (78%). Compared with all samples, Bayesian AUC estimation with optimal samples had a mean bias of 0.4% (±5.9%) and mean imprecision of 4.6% (±3.6%). Bias of optimal sampling was <10% for 17 of the 18 participants (94%). When estimating AUC using only a peak sample (≤2 hours after dose) or only a trough (≤30 minutes before next dose), bias was <10% for 78% and 86% of participants, respectively.
Conclusions: Optimal sampling supports accurate Bayesian estimation of vancomycin AUC from a single plasma sample in critically ill children.
期刊介绍:
Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.