Dose optimization of piperacillin/tazobactam in patients with renal dysfunction based on population pharmacokinetic and pharmacodynamic simulations  

基于群体药动学和药效学的仿真对肾功能不全病人使用哌拉西林/他唑巴坦进行剂量优化（英文）

作　　者：Chao Zhang Ruohan Xie Chuhui Wang Chenchen Xi Mengjia Ge 张弨;谢若函;王楚慧;袭辰辰;戈梦佳(北京大学第三医院药剂科,北京100191;国家食品药品监督管理总局药品审评中心,北京100022)

机构地区：[1]Department of pharmacy, Peking University Third Hospital, Beijing 100191, China [2]Center for drug evaluation, China Food and Drug Administration, Beijing 100053, China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2018年第12期824-831,共8页中国药学（英文版）

基　　金：Peking University Third Hospital research funding(Grant No.7476-01)

摘　　要：In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial resistance. A total of 2700 simulationswere applied based on a published population pharmacokinetic and pharmacodynamic model using nonlinear mixed effects modeling (NONMEM) software. Permissible optimal dosage regimens were defined as those associated with a less than 10% of patients whose probabilities of target attainment (PTA) were not attain target. For patients with mild to moderate renal injury, 4/0.5 g of piperacillin/tazobactam every 12 h in 30 min intermittent infusion could attain the target. If the MIC (minimum inhibitory concentration) for the pathogen was 8 mg/L or 16 mg/L, either an 8-h or 6-h dosing interval or extended 2–6 h infusion regimen had to be used to achieve the outcome of the therapy. Regarding MIC was up to above 32 mg/L, a high dose of piperacillin (12–24 g/d) in continuous infusion was the only approach that could achieve the effective target in patients with renal dysfunction. A low dose with extended 4–6 h infusion regimen was recommended for patients with severe renal injury. Our study identified permissible optimal piperacillin/tazobactam dosage regimens for patients with renal dysfunction with an MIC up to 64 mg/L. The findings of this study would be helpful for precise administration of piperacillin/tazobactam in clinical practice.本研究的目的是根据患者不同程度的肾功能损伤和细菌耐药情况,探索哌拉西林/他唑巴坦在肾功能不全患者中的给药方案。本研究基于已发表的群体药动学模型,使用非线性混合效应模型(NONMEM)法进行2700次的仿真,最佳的给药方案定义为不达标的患者的概率低于10%。研究发现对于肾功能轻度至中度损害的患者,常规4/0.5g哌拉西林/他唑巴坦, q12h, 30 min给药方案是合适的。但当MIC为8 mg/L或16 mg/L时,需要调整给药方案为q8h或q6h或者延长输注时间为2–6 h。当MIC大于32 mg/L时, 12–24g/天的高剂量哌拉西林持续输注是唯一可以达到目标值的给药方案。对于严重肾损伤的病人,推荐采用低剂量并延长输注4–6h。本研究中给出不同MIC(直到64 mg/L)下,肾功能不全患者给予哌拉西林/他唑巴坦的具体推荐给药方案,研究结果将会为哌拉西林/他唑巴坦在临床上的精确给药提供帮助。

关 键 词：PIPERACILLIN/TAZOBACTAM Renal dysfunction Dose optimization 

分 类 号：R954[医药卫生—药学]