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

doi:10.5246/jcps.2018.12.083

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (12): 824-831.DOI: 10.5246/jcps.2018.12.083

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

张弨^1*, 谢若函¹, 王楚慧¹, 袭辰辰², 戈梦佳¹

1. 北京大学第三医院药剂科, 北京 100191
2. 国家食品药品监督管理总局药品审评中心, 北京 100022

收稿日期:2018-07-25 修回日期:2018-10-05 出版日期:2018-12-30 发布日期:2018-11-06
通讯作者: Tel./Fax: +86+010-82266673, E-mail: laural.zhang@yahoo.com
基金资助:
Peking University Third Hospital research funding (Grant No. 7476-01).

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

Chao Zhang^1*, Ruohan Xie¹, Chuhui Wang¹, Chenchen Xi², Mengjia Ge¹

1. Department of pharmacy, Peking University Third Hospital, Beijing 100191, China
2. Center for drug evaluation, China Food and Drug Administration, Beijing 100053, China

Received:2018-07-25 Revised:2018-10-05 Online:2018-12-30 Published:2018-11-06
Contact: Tel./Fax: +86+010-82266673, E-mail: laural.zhang@yahoo.com
Supported by:
Peking University Third Hospital research funding (Grant No. 7476-01).

摘要/Abstract

摘要：

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4/0.5 g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, 12–24 g/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4–6 h。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: 哌拉西林/他唑巴坦, 肾功能不全, 剂量优化

Abstract:

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.

Key words: Piperacillin/tazobactam, Renal dysfunction, Dose optimization

中图分类号:

R954

Supporting:

张弨, 谢若函, 王楚慧, 袭辰辰, 戈梦佳. 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[J]. 中国药学(英文版), 2018, 27(12): 824-831.

Chao Zhang, Ruohan Xie, Chuhui Wang, Chenchen Xi, Mengjia Ge. Dose optimization of piperacillin/tazobactam in patients with renal dysfunction based on population pharmacokinetic and pharmacodynamic simulations[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(12): 824-831.

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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

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

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