在儿科患者中使用一阶药代动力学方法估算万古霉素的 AUC0-24。

IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacotherapy Pub Date : 2024-04-01 Epub Date: 2024-03-27 DOI:10.1002/phar.2916
Hope H Brandon, David S Burgess, Katie L Wallace, Elizabeth B Autry, Katie B Olney
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引用次数: 0

摘要

简介:万古霉素在儿科的最佳剂量和监测方法尚不清楚,但已逐渐发展为强调 24 小时内的曲线下面积(AUC0-24)而非最低浓度(Cmin)监测。在儿科患者中,尚缺乏支持双浓度动力学一阶方程估算万古霉素 AUC0-24 的可行性的实际数据:目的:在四个儿科年龄组中使用一阶方程描述万古霉素剂量、AUC0-24 和 Cmin 的相互作用:这是一项单中心、回顾性队列研究,分析对象为儿科患者(0-24 岁):共有 219 名患者(中位年龄为 6 岁 [IQR 1-12])符合纳入标准。新生儿万古霉素日剂量中位数为 30 毫克/千克,婴儿和儿童为 70 毫克/千克,青少年为 52 毫克/千克。各年龄组的中位 Cmin 值和 AUC0-24 值分别为 8.68 毫克/升和 505 毫克*小时/升。在治疗范围(400-600 毫克 * 小时/升)之外的 AUC0-24 值中,超治疗值(>600 毫克 * 小时/升)多于低治疗值(Cmin 和 AUC0-24)。然而,在 Cmin 值为 5-10 mg/L 的患者中,71% 的 AUC0-24 值在 400-600 mg * h/L 的治疗范围内,而 AUC0-24 值为 SUPRA 治疗值的 23 名患者(92%)的 Cmin 值≥15 mg/L。约 10% 的患者出现急性肾损伤:我们的数据描述了儿童患者中万古霉素剂量、Cmin 和 AUC0-24 之间的关系。我们证明了使用一阶方程估算 AUC0-24 的可行性,利用稳态时获得的两个浓度来监测静脉注射万古霉素的儿科患者的疗效和安全性。我们的数据显示 AUC0-24 与 Cmin 之间的相关性不理想,这表明 Cmin 不应作为儿科患者治疗 AUC0-24 的替代指标。根据 2020 年万古霉素共识指南,我们建议使用 AUC0-24 进行疗效和安全性监测。
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Vancomycin AUC0-24 estimation using first-order pharmacokinetic methods in pediatric patients.

Introduction: The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC0-24) over minimum concentration (Cmin) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC0-24 in pediatric patients are lacking.

Objectives: To describe the interplay of vancomycin dose, AUC0-24, and Cmin using first-order equations within four pediatric age groups.

Methods: This is a single-center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1-12 years), and adolescents (13-17 years). First-order equations were utilized to estimate pharmacokinetic parameters and AUC0-24.

Results: Overall, 219 patients (median age of 6 years [IQR 1-12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median Cmin and AUC0-24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC0-24 values outside of the therapeutic range (400-600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between Cmin and AUC0-24. However, 71% of patients with Cmin values of 5-10 mg/L had an AUC0-24 within the therapeutic range of 400-600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC0-24 had a Cmin value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury.

Conclusions: Our data describe the relationship between vancomycin dose, Cmin, and AUC0-24 in pediatric patients. We demonstrated the feasibility of using first-order equations to estimate AUC0-24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC0-24 and Cmin, which indicates that Cmin should not be used as a surrogate marker for a therapeutic AUC0-24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC0-24 for efficacy and safety monitoring.

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来源期刊
Pharmacotherapy
Pharmacotherapy 医学-药学
CiteScore
7.80
自引率
2.40%
发文量
93
审稿时长
4-8 weeks
期刊介绍: Pharmacotherapy is devoted to publication of original research articles on all aspects of human pharmacology and review articles on drugs and drug therapy. The Editors and Editorial Board invite original research reports on pharmacokinetic, bioavailability, and drug interaction studies, clinical trials, investigations of specific pharmacological properties of drugs, and related topics.
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