Bayesian Vancomycin Model Selection for Therapeutic Drug Monitoring in Neonates.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Clinical Pharmacokinetics Pub Date : 2024-03-01 Epub Date: 2024-02-28 DOI:10.1007/s40262-024-01353-8
Dua'a Alrahahleh, Yann Thoma, Ruth Van Daele, Thi Nguyen, Stephanie Halena, Melissa Luig, Sophie Stocker, Hannah Yejin Kim, Jan-Willem Alffenaar
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Abstract

Background and objective: Pharmacokinetic models can inform drug dosing of vancomycin in neonates to optimize therapy. However, the model selected needs to describe the intended population to provide appropriate dose recommendations. Our study aims to identify the population pharmacokinetic (PopPK) model(s) with the best performance to predict vancomycin exposure in neonates in our hospital.

Methods: Relevant published PopPK models for vancomycin in neonates were selected based on demographics and vancomycin dosing strategy. The predictive performance of the models was evaluated in Tucuxi using a local cohort of 69 neonates. Mean absolute error (MAE), relative bias (rBias) and relative root mean square error (rRMSE) were used to quantify the accuracy and precision of the predictive performance of each model for three different approaches: a priori, a posteriori, and Bayesian forecasting for the next course of therapy based on the previous course predictions. A PopPK model was considered clinically acceptable if rBias was between ± 20 and 95% confidence intervals included zero.

Results: A total of 25 PopPK models were identified and nine were considered suitable for further evaluation. The model of De Cock et al. 2014 was the only clinically acceptable model based on a priori [MAE 0.35 mg/L, rBias 0.8 % (95% confidence interval (CI) - 7.5, 9.1%), and rRMSE 8.9%], a posteriori [MAE 0.037 mg/L, rBias - 0.23% (95% CI - 1.3, 0.88%), and rRMSE 6.02%] and Bayesian forecasting for the next courses [MAE 0.89 mg/L, rBias 5.45% (95% CI - 8.2, 19.1%), and rRMSE 38.3%) approaches.

Conclusions: The De Cock model was selected based on a comprehensive approach of model selection to individualize vancomycin dosing in our neonates.

Abstract Image

用于新生儿治疗药物监测的贝叶斯万古霉素模型选择。
背景和目的:药代动力学模型可为新生儿万古霉素的用药剂量提供依据,以优化治疗。然而,所选模型需要描述目标人群,以提供适当的剂量建议。我们的研究旨在确定性能最佳的群体药代动力学(PopPK)模型,以预测本院新生儿的万古霉素暴露量:方法:根据人口统计学和万古霉素给药策略,选择已发表的相关新生儿万古霉素流行药代动力学模型。在土库西使用当地的 69 例新生儿队列评估了模型的预测性能。平均绝对误差 (MAE)、相对偏差 (rBias) 和相对均方根误差 (rRMSE) 被用来量化每个模型在三种不同方法下预测性能的准确性和精确性:先验法、后验法和基于前一疗程预测的贝叶斯法预测下一疗程。如果rBias在±20之间,且95%置信区间为零,则PopPK模型被认为是临床可接受的:结果:共确定了 25 个 PopPK 模型,其中 9 个适合进一步评估。根据先验[MAE 0.35 mg/L,rBias 0.8 %(95% 置信区间 (CI) - 7.5,9.1%),rRMSE 8.9%]、后验[MAE 0.037 mg/L,rBias - 0.23% (95% CI - 1.3, 0.88%),rRMSE 6.02%],以及贝叶斯预测下一疗程[MAE 0.89 mg/L,rBias 5.45% (95% CI - 8.2, 19.1%),rRMSE 38.3%]的方法:根据模型选择的综合方法,我们选择了 De Cock 模型来为新生儿个体化万古霉素剂量。
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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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