Lexnoi Tanisa, Boonpeng Apinya, Santimaleeworagun Wichai, Chaisiri Kessarin, Dechsanga Jutamas, Vattanavanit Veerapong, Ungthammakhun Chutchawan, Sitaruno Sirima
Division of Clinical Pharmacy, Department of Pharmacy, Chonburi Hospital, Muang, Chonburi, Thailand.
School of Pharmaceutical Sciences, University of Phayao, Muang, Phayao, Thailand.
J Clin Pharmacol. 2025 Aug;65(8):970-979. doi: 10.1002/jcph.70009. Epub 2025 Feb 18.
Pathophysiologic changes in the early and late phases of septic shock affect the pharmacokinetic (PK) parameters, varying dose adjustments may be necessary. This study aimed to create the PK models of vancomycin in the early and late phases of septic shock and to describe the association between the area under the curve from 0 to 24 h (AUC) and acute kidney injury (AKI). The data from patients with septic shock receiving vancomycin was collected either prospectively or retrospectively. A nonlinear mixed-effects modeling approach was used to develop the PK models. A total of 208 septic shock patients were enrolled and classified into the early (n = 96) and the late phase (n = 112). A two-compartment PK model is the best base model for both phases of septic shock. The model that best predicted the clearance (CL) of both phases was the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, which was not indexed to body surface area (BSA). Albumin (ALB) was a covariate associated with vancomycin CL only in the late phase. The typical values of CL and volume of distribution (V) in the early phase were 1.71 L/h and 68.94 L. In the late phase, CL was 1.65 L/h, and V was 66.36 L. The AKI was observed in patients with a high simulated AUC. The population PK model of vancomycin in the early and late phases of septic shock has been established. The CKD-EPI not indexed to BSA predicts vancomycin CL in both phases. ALB was associated with CL in the late phase.
脓毒症休克早期和晚期的病理生理变化会影响药代动力学（PK）参数，可能需要进行不同的剂量调整。本研究旨在建立万古霉素在脓毒症休克早期和晚期的PK模型，并描述0至24小时曲线下面积（AUC）与急性肾损伤（AKI）之间的关联。收集了接受万古霉素治疗的脓毒症休克患者的前瞻性或回顾性数据。采用非线性混合效应建模方法建立PK模型。共纳入208例脓毒症休克患者，分为早期（n = 96）和晚期（n = 112）。两室PK模型是脓毒症休克两个阶段的最佳基础模型。最能预测两个阶段清除率（CL）的模型是2021年慢性肾脏病流行病学协作组（CKD - EPI）肌酐方程，该方程未根据体表面积（BSA）进行校正。白蛋白（ALB）仅在晚期是与万古霉素CL相关的协变量。早期CL和分布容积（V）的典型值分别为1.71 L/h和68.94 L。晚期，CL为1.65 L/h，V为66.36 L。在模拟AUC较高的患者中观察到AKI。已建立万古霉素在脓毒症休克早期和晚期的群体PK模型。未根据BSA校正的CKD - EPI可预测两个阶段的万古霉素CL。ALB在晚期与CL相关。
