Yokoyama Yuta, Matsumoto Kazuaki, Ikawa Kazuro, Watanabe Erika, Morikawa Norifumi, Takeda Yasuo
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan; Department of Clinical Pharmacotherapy, Hiroshima University, Japan.
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
J Infect Chemother. 2015 Apr;21(4):284-9. doi: 10.1016/j.jiac.2014.12.005. Epub 2014 Dec 26.
This study aimed to perform a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of sulbactam against Acinetobacter baumannii in patients with impaired renal function. The PK data (188 plasma samples and 27 urine samples) were modeled simultaneously. The mean population parameters were CLr (l/h) = 0.0792 × CLcr (ml/min), CLnr (l/h) = 2.35, Vc (l) = 12.2, Q (l/h) = 4.68 and Vp (l) = 4.44, where CLr and CLnr are the renal and non-renal clearances, Vc and Vp are the distribution volumes of the central and peripheral compartments and Q is intercompartmental clearance. The creatinine clearance (CLcr) was the most significant covariate. The determined MIC of sulbactam against A. baumannii clinical isolates (n = 27) was 0.75-6.0 μg/ml with MIC50 and MIC90 of 1 and 4 μg/ml, respectively. For sulbactam regimens, a Monte Carlo simulation estimated the probabilities of attaining the bactericidal target (60% of the time above the MIC) and determined the PK-PD breakpoints (the highest MICs at which the probabilities were 90% or more). In a patient with a CLcr of 15 ml/min, a regimen of 1 g twice daily achieved a 90% or more probability against the A. baumannii isolate population; however, 2 g four times daily was needed for a 90% or more probability in a patient with a CLcr of 90 ml/min. The results of the PK-PD target attainment analysis are useful when choosing the sulbactam regimen based on the CLcr of the patient and the susceptibility of A. baumannii.
UMIN000007356.
本研究旨在对肾功能受损患者中舒巴坦针对鲍曼不动杆菌进行药代动力学（PK）-药效学（PD）目标达成分析。同时对PK数据（188份血浆样本和27份尿液样本）进行建模。总体平均参数为CLr（升/小时）=0.0792×CLcr（毫升/分钟），CLnr（升/小时）=2.35，Vc（升）=12.2，Q（升/小时）=4.68以及Vp（升）=4.44，其中CLr和CLnr分别为肾脏和非肾脏清除率，Vc和Vp分别为中央室和外周室的分布容积，Q为室间清除率。肌酐清除率（CLcr）是最显著的协变量。舒巴坦针对鲍曼不动杆菌临床分离株（n = 27）的测定MIC为0.75 - 6.0微克/毫升，MIC50和MIC90分别为1和4微克/毫升。对于舒巴坦治疗方案，蒙特卡洛模拟估计了达到杀菌目标（60%的时间高于MIC）的概率，并确定了PK-PD断点（概率为90%或更高时的最高MIC）。在CLcr为15毫升/分钟的患者中，每日两次1克的治疗方案对鲍曼不动杆菌分离株群体达到90%或更高概率；然而，在CLcr为90毫升/分钟的患者中，每日四次2克的治疗方案才能达到90%或更高概率。基于患者的CLcr和鲍曼不动杆菌的敏感性选择舒巴坦治疗方案时，PK-PD目标达成分析结果很有用。
UMIN000007356。
