Kim Jong Hyun, Lah Hyon-Oh, Yim Dong-Seok
Department of Surgery, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, South Korea.
Eur J Clin Pharmacol. 2008 Jun;64(6):599-603. doi: 10.1007/s00228-008-0470-1.
The aim of this study was to estimate the pharmacokinetics (PK) of arbekacin in burn patients using a population-PK approach. Therapeutic drug monitoring data consisting of 126 plasma concentrations (including 17 values that were below the quantitation limit) from 47 burn patients were retrospectively analyzed using a mixed effect method (NONMEM, ver. 6.0). Covariates, such as burn index, age, sex, among others, were tested on the basic one-compartment model. In the basic model, positive correlations of body weight (WT) and creatinine clearance (CLcr) on total clearance (CL) and volume of distributions (V) were assumed. In the final model, V increased with burn index (BI). The final model was: CL(L/h) = 3.18x WT/ 70 + 4.49x CLcr/120; V(L) = 27.5x WT/70 + 0.28x (BI-23.5). Between-subject variability in terms of CL and V were 35 and 39%, respectively. The CL of our burn patients was significantly greater than that reported in unburned patients, and V increased proportionally with increasing BI.
本研究的目的是采用群体药代动力学方法估算烧伤患者中阿贝卡星的药代动力学（PK）。使用混合效应方法（NONMEM，版本6.0）对47例烧伤患者的126个血浆浓度（包括17个低于定量限的值）的治疗药物监测数据进行回顾性分析。在基本的一室模型上测试了诸如烧伤指数、年龄、性别等协变量。在基本模型中，假设体重（WT）和肌酐清除率（CLcr）与总清除率（CL）和分布容积（V）呈正相关。在最终模型中，V随烧伤指数（BI）增加。最终模型为：CL（L/h）=3.18×WT/70 + 4.49×CLcr/120；V（L）=27.5×WT/70 + 0.28×（BI - 23.5）。CL和V的个体间变异性分别为35%和39%。我们烧伤患者的CL显著高于未烧伤患者报告的CL，且V随BI增加而成比例增加。
