Department of Pharmacy Practice & Science and Department of Medicine, University of Arizona, Tucson, AZ, USA.
Department of Pharmacy Practice & Science, University of Arizona, Tucson, AZ, USA.
Am J Health Syst Pharm. 2022 Mar 21;79(7):534-539. doi: 10.1093/ajhp/zxab457.
Prior to the 2020 release of a joint consensus guideline on monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, clinicians had escalated vancomycin doses for 2 decades while targeting trough concentrations of 15 to 20 µg/mL, leading to an increased frequency of nephrotoxicity. For MRSA infections, the 2020 guideline recommends adjusting doses to achieve a 24-hour area under the concentration-time curve (AUC) of 400 to 600 µg · h/mL; however, monitoring of trough concentrations has been entrenched for 3 decades. Calculating dose regimens based on AUC will require obtaining an increased number of vancomycin serum concentrations and, possibly, advanced software. The aim of this investigation was to determine the relationship between AUC and trough concentration and the influence of dosing regimen on goal achievement.
The relationship between trough concentration and AUC was explored through derivation of an equation based on a 1-compartment model and simulations.
24-hour AUC is related to dosing interval divided by half-life in a nonlinear fashion. The target trough concentration can be individualized to achieve a desired AUC range, and limiting use of large doses (>15-20 mg/kg) can protect against excessive 24-hour AUC with trough-only monitoring.
After initially determining pharmacokinetic parameters, subsequent monitoring of AUC can be accomplished using trough concentrations only. Trough concentration may be used as a surrogate for AUC, although the acceptable target trough concentration will vary depending on dosing interval and elimination rate constant. This work included development of an AUC-trough equation to establish a patient-specific target for steady-state trough concentration.
在 2020 年发布关于监测严重耐甲氧西林金黄色葡萄球菌 (MRSA) 感染万古霉素治疗的联合共识指南之前，临床医生在 20 年内一直在提高万古霉素剂量，同时将谷浓度目标设定在 15 至 20μg/mL，导致肾毒性的发生率增加。对于 MRSA 感染，2020 年指南建议调整剂量以实现 24 小时浓度-时间曲线下面积 (AUC) 为 400 至 600μg·h/mL；然而，谷浓度监测已经根深蒂固了 30 年。基于 AUC 计算剂量方案将需要获得更多的万古霉素血清浓度，并且可能需要使用先进的软件。本研究旨在确定 AUC 与谷浓度之间的关系以及剂量方案对目标达成的影响。
通过基于单室模型的方程推导和模拟来探索谷浓度与 AUC 之间的关系。
24 小时 AUC 与剂量间隔除以半衰期呈非线性关系。可以将目标谷浓度个体化以实现所需的 AUC 范围，并且限制使用大剂量 (>15-20mg/kg) 可以防止仅通过谷浓度监测导致 24 小时 AUC 过高。
在最初确定药代动力学参数后，仅使用谷浓度即可监测 AUC。谷浓度可以作为 AUC 的替代物，尽管可接受的目标谷浓度将根据剂量间隔和消除速率常数而有所不同。这项工作包括开发 AUC-谷浓度方程，以确定稳态谷浓度的患者特定目标。
