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Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (12): 824-831.DOI: 10.5246/jcps.2018.12.083

• Original articles • Previous Articles     Next Articles

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

Chao Zhang1*, Ruohan Xie1, Chuhui Wang1, Chenchen Xi2, Mengjia Ge1   

  1. 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).

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 26 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

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