Kim Yong Kyun, Jung Jin Ah, Choi Hyang Ki, Bae In Gyu, Choi Won Suk, Hur Jian, Jin Sung Joon, Kim Shin Woo, Kwon Ki Tae, Lee Sang Rok, Shin Jae Gook, Kiem Sungmin
Division of Infectious Diseases, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
Department of Clinical Pharmacology, Inje University College of Medicine, Busan, Korea.
Infect Chemother. 2016 Sep;48(3):209-215. doi: 10.3947/ic.2016.48.3.209. Epub 2016 Sep 6.
For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients' characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections.
At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) ≤50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P < 0.05 for selection and P < 0.01 for elimination.
Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CL(cr) /47 for piperacillin and CL = 1.76 + 4.81 × CL(cr) /47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam.
The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance.
为了更有效、更安全地使用抗生素，给药策略应根据患者的特征（包括种族）进行个体化。本研究的目的是调查哌拉西林和他唑巴坦在韩国急性感染患者中的群体药代动力学（PK）特征。
肌酐清除率（CL(cr)）≤50 ml/min或CL(cr)>50 mL/min的患者，分别每8小时静脉输注至少4剂2/0.25 g或4/0.5 g哌拉西林/他唑巴坦（TZP），持续1小时。在稳态下，采集33例患者给药前以及第四次输注后0分钟、30分钟和4 - 6小时的血样。采用非线性混合效应方法进行群体PK分析。使用似然比检验选择显著协变量，选择的显著性水平为P < 0.05，剔除的显著性水平为P < 0.01。
哌拉西林PK和他唑巴坦PK均由具有一级消除的二室模型很好地描述。在可能影响两种药物PK参数的协变量中，选择肌酐清除率和体重作为清除率（CL）和中央室容积（V1）的协变量。哌拉西林的CL定义为CL = 2.9 + 4.03 × CL(cr) /47，他唑巴坦的CL定义为CL = 1.76 + 4.81 × CL(cr) /47。哌拉西林的V1定义为V1 = 19.5 ×体重/60，他唑巴坦的V1定义为V1 = 22.6 ×体重/60。
具有一级消除的二室模型很好地描述了韩国急性感染患者稳态下TZP的PK特征。哌拉西林和他唑巴坦的清除率均受肌酐清除率的显著影响。
