通过贝叶斯模拟万古霉素个体给药方案:对早产儿和足月新生儿的5年回顾性研究。

Lu Tan, Ailing Chao, Heng Liang, Qian Liu, Minzhen Han, Yanping Guan
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引用次数: 0

摘要

目的:万古霉素在新生儿的剂量是具有挑战性的,由于发育药代动力学变异性。该研究旨在描述万古霉素在大量早产儿和足月新生儿中的药代动力学特征,并制定个性化的给药方案。材料与方法:对255名新生儿进行了为期5年的回顾性研究。结果:一阶消除异速速单室模型最能描述万古霉素浓度。清除率(CL)和分布体积(V)的群体药代动力学估计值(受试者变异性之间)分别为2.58 L·h-1·70 kg-1(9.00%)和52.09 L·70 kg-1(29.00%)。体重和经后年龄对CL和V有显著影响。万古霉素CL在妊娠43.6周时达到成人值的50%(乙状结肠Emax模型)。肾成熟度,通过肌酐生成率来估计,是一个显著的协变量。开发并评估了贝叶斯指导的个体化给药方案。结论:非常年幼的早产儿(PMA = 25周)应避免万古霉素过量。需要优化万古霉素对早产儿和足月新生儿的疗效,同时尽量减少其毒性,特别是在个性化体重、经后年龄和肾功能的指导下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Vancomycin individual dosing regimens via Bayesian simulation: a 5-year retrospective study on preterm and term neonates.

Aim: Vancomycin dosing in neonates is challenging due to developmental pharmacokinetic variability. The study was to characterize vancomycin pharmacokinetics in a large cohort of preterm and term neonates and develop individualized dosing regimens.

Materials & methods: A 5-year retrospective study of a cohort of 255 neonates was included.

Results: An allometric one-compartment model with first-order elimination best described the vancomycin concentrations. The population pharmacokinetic estimates (between subject variability) of clearance (CL) and volume of distribution (V) were 2.58 L·h-1·70 kg-1 (9.00 %) and 52.09 L·70 kg-1 (29.00%), respectively. CL and V were significantly influenced by body weight and postmenstrual age. Vancomycin CL reached 50% of adult values at 43.6 weeks PMA (a sigmoid Emax model). Renal maturation, estimated by creatinine production rate, was a significant covariate. Bayesian-guided individualized dosage regimens were developed and evaluated.

Conclusions: Vancomycin overdosage should be avoided in very young premature babies (PMA = 25 weeks). Optimization of efficacy while minimizing toxicity of vancomycin in preterm and term neonates is needed, especially guided by personalized body weight, postmenstrual age, and renal function.

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