Yi Jung-Min, Kim Kyung Mi, Lee Hak-Jae, Hong Suk-Kyung, Choi Byung-Moon
Department of Anesthesiology and Pain Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea.
Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Drug Des Devel Ther. 2025 Mar 24;19:2229-2241. doi: 10.2147/DDDT.S507377. eCollection 2025.
Target-controlled infusion (TCI) could provide a patient-tailored approach for vancomycin dosing. This study aimed to externally evaluate the predictive performance of a previously constructed pharmacokinetic model of vancomycin (Choi model) specifically optimized for TCI administration of vancomycin differing from the existing model, and to assess the feasibility of administering vancomycin via TCI in clinical practice. Additionally, clinical outcomes were exploratively compared between the TCI and intermittent infusion (standard) methods for vancomycin administration.
Clinically ill patients were randomly assigned in a 1:1 ratio to either the TCI or standard group. In the TCI group, vancomycin was administered using the Choi model, targeting an initial concentration of 25 mg/L, adjusted to maintain therapeutic levels (20-30 mg/L). The standard group received a loading dose of 25 mg/kg, then 15 mg/kg every 12 hours. Vancomycin concentrations for analysis were obtained from three blood samples per patient at set times, along with routine therapeutic drug monitoring data. Predictive performance was assessed using four parameters: inaccuracy, divergence, bias, and wobble. The occurrence of acute kidney injury (AKI) during and up to 7 days after vancomycin was investigated.
The study was terminated early due to challenges in enrolling subjects (TCI: n=12, standard: n=13). Thirty-seven serum concentration measurements from the TCI group were analyzed. Pooled median bias and inaccuracy (95% confidence interval) were -2.7 (-7.3 to 1.9) and 17.0 (13.9 to 20.2), respectively. AKI incidence was similar between groups (TCI: n=0, standard: n=1) in this exploratory analysis, but caution is warranted in interpreting these outcomes as the planned sample size was not met.
The predictive performance of the TCI system integrated with the Choi model was suitable for clinical use. Further studies with a large cohort should be performed to determine the clinical effectiveness of vancomycin administered via the TCI method.
This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http://cris.nih.go.kr), with registration number KCT0003462, on January 31, 2019).
靶控输注（TCI）可为万古霉素给药提供个体化方法。本研究旨在对外评估先前构建的针对万古霉素TCI给药专门优化的万古霉素药代动力学模型（Choi模型）的预测性能，该模型不同于现有模型，并评估在临床实践中通过TCI给予万古霉素的可行性。此外，还对万古霉素给药的TCI和间歇输注（标准）方法的临床结局进行了探索性比较。
临床疾病患者按1:1比例随机分为TCI组或标准组。在TCI组中，使用Choi模型给予万古霉素，目标初始浓度为25mg/L，并进行调整以维持治疗水平（20 - 30mg/L）。标准组接受25mg/kg的负荷剂量，然后每12小时给予15mg/kg。在设定时间从每位患者采集三份血样以获取用于分析的万古霉素浓度，以及常规治疗药物监测数据。使用四个参数评估预测性能：不准确性、偏差、偏倚和摆动。研究了万古霉素给药期间及给药后7天内急性肾损伤（AKI）的发生情况。
由于招募受试者存在困难，该研究提前终止（TCI组：n = 12，标准组：n = 13）。分析了TCI组的37次血清浓度测量值。合并的中位数偏倚和不准确性（95%置信区间）分别为 - 2.7（ - 7.3至1.9）和17.0（13.9至20.2）。在这项探索性分析中，两组间AKI发生率相似（TCI组：n = 0，标准组：n = 1），但由于未达到计划样本量，在解释这些结果时应谨慎。
与Choi模型整合的TCI系统的预测性能适用于临床使用。应进行更大队列的进一步研究以确定通过TCI方法给予万古霉素的临床有效性。
本研究于2019年1月31日在韩国国立卫生研究院临床研究信息服务中心（CRIS，http://cris.nih.go.kr）注册（注册号KCT0003462）。
