Oshima Yuki, Matsumoto Miyu, Munakata Sumika, Tokimatsu Issei, Hattori Norimichi, Kotani Toru, Kusumoto Sojiro, Sagara Hironori, Kato Masaru
Division of Bioanalytical Chemistry, Department of Pharmaceutical Sciences, Showa University Graduate School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan.
Department of Bioanalytical Chemistry, School of Pharmacy, Showa University, Tokyo, Japan.
AAPS J. 2025 Feb 4;27(1):39. doi: 10.1208/s12248-025-01021-0.
Therapeutic drug monitoring (TDM) is recommended during vancomycin (VCM) administration to adjust the dosage such that the area under the curve (AUC) remains between 400 and 600 µg·h/mL (minimum inhibitory concentration = 1 µg/mL). However, measuring the AUC requires frequent blood sampling, which increases the burden of added time and cost for testing on both patients and healthcare personnel. Therefore, we aimed to address these issues by developing a simple and rapid method for measuring urinary VCM levels using solid-phase extraction and fluorescence spectrometry. The developed method had a quantification range of 100-2,000 µg/mL, with an accuracy of 100.0%-108.5% for concentrations of 200, 1,000, and 2,000 µg/mL. The intra- and inter-day relative standard deviations were below 3.39% and 4.48%, respectively. Furthermore, to predict the AUC from urinary VCM concentrations, we calculated the slope of the urinary concentrations at 7-12 h post-VCM administration in six patients. The slope for one patient differed significantly from that for the others, and the AUC was obtained using practical AUC-guided TDM for vancomycin (PAT) ver. 3.0c for the patient whose value deviated from the recommended range. A negative correlation was observed between the slope and AUC, with a correlation coefficient of 0.65, suggesting the potential for predicting AUC from urinary concentration trends. The use of urine samples, which can be easily obtained, for VCM dose adjustment is expected to contribute to providing more appropriate drug therapy to patients and reduce the burden on healthcare professionals.
在使用万古霉素(VCM)治疗期间,建议进行治疗药物监测(TDM)以调整剂量,使曲线下面积(AUC)保持在400至600µg·h/mL之间(最低抑菌浓度=1µg/mL)。然而,测量AUC需要频繁采血,这增加了患者和医护人员的检测时间和成本负担。因此,我们旨在通过开发一种使用固相萃取和荧光光谱法测量尿VCM水平的简单快速方法来解决这些问题。所开发的方法定量范围为100 - 2000µg/mL,对于200、1000和2000µg/mL的浓度,准确度为100.0% - 108.5%。日内和日间相对标准偏差分别低于3.39%和4.48%。此外,为了从尿VCM浓度预测AUC,我们计算了6名患者在VCM给药后7 - 12小时尿浓度的斜率。一名患者的斜率与其他患者有显著差异,对于其值偏离推荐范围的患者,使用万古霉素实用AUC指导TDM(PAT)ver. 3.0c获得了AUC。观察到斜率与AUC之间呈负相关,相关系数为0.65,表明有可能从尿浓度趋势预测AUC。使用易于获取的尿样进行VCM剂量调整有望有助于为患者提供更合适的药物治疗,并减轻医护人员的负担。