Shahrami Bita, Najmeddin Farhad, Ghaffari Saeideh, Najafi Atabak, Rouini Mohammad Reza, Mojtahedzadeh Mojtaba
Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Crit Care Res Pract. 2020 Dec 24;2020:8831138. doi: 10.1155/2020/8831138. eCollection 2020.
The area under the curve- (AUC-) guided vancomycin dosing is the best strategy for individualized therapy in critical illnesses. Since AUC can be calculated directly using drug clearance (CL), any parameter estimating CL will be able to achieve the goal of 24-hour AUC (AUC). The present study was aimed to determine CL based on 6-hour urine creatinine clearance measurement in critically ill patients with normal renal function.
23 adult critically ill patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min who received vancomycin infusion were enrolled in this pilot study. Vancomycin pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model provided by MONOLIX software using stochastic approximation expectation-maximization (SAEM) algorithm. Correlation of CL with the measured creatinine clearance in 6-hour urine collection (CL) and estimated creatinine clearance by the Cockcroft-Gault formula (CL) was investigated.
Data analysis revealed that CL had a stronger correlation with CL rather than CL ( = 0.823 vs. 0.594; < 0.001 vs. 0.003). The relationship between CL and CL was utilized to develop the following equation for estimating CL: CL (mL/min) = ─137.4 + CL (mL/min) + 2.5 IBW (kg) ( = 0.826, < 0.001). Regarding the described model, the following equation can be used to calculate the empirical dose of vancomycin for achieving the therapeutic goals in critically ill patients without renal impairment: total daily dose of vancomycin (mg) = (─137.4CL (mL/min) + 2.5 IBW (kg)) × 0.06 AUC (mg.hr/L).
For AUC estimation, CL can be obtained by collecting urine in a 6-hour period with good approximation in critically ill patients with normal renal function.
曲线下面积（AUC）指导的万古霉素给药是危重症个体化治疗的最佳策略。由于AUC可直接使用药物清除率（CL）计算，任何估算CL的参数都能够实现24小时AUC（AUC）的目标。本研究旨在通过测量肾功能正常的危重症患者6小时尿肌酐清除率来确定CL。
本前瞻性研究纳入了23例接受万古霉素输注、估计肾小球滤过率（eGFR）≥60 mL/min的成年危重症患者。使用血清浓度数据和由MONOLIX软件提供的一室模型，采用随机近似期望最大化（SAEM）算法，为每位患者确定万古霉素药代动力学参数。研究CL与6小时尿液收集测得的肌酐清除率（CL）以及Cockcroft-Gault公式估算的肌酐清除率（CL）之间的相关性。
数据分析显示，CL与CL的相关性强于与CL的相关性（分别为r = 0.823对0.594；P < 0.001对0.003）。利用CL与CL之间的关系建立了以下估算CL的方程：CL（mL/min）= ─137.4 + CL（mL/min）+ 2.5×理想体重（kg）（r = 0.826，P < 0.001）。对于所描述的模型，可使用以下方程计算无肾功能损害的危重症患者达到治疗目标所需的万古霉素经验性剂量：万古霉素每日总剂量（mg）=（─137.4×CL（mL/min）+ 2.5×理想体重（kg））×0.06×AUC（mg·hr/L）。
对于AUC估算，在肾功能正常的危重症患者中，通过收集6小时尿液可较好地近似获得CL。
