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

doi:10.5246/jcps.2018.12.083

Abstract

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

CLC Number:

R954

Supporting:

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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