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Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses

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Abstract

Piperacillin-tazobactam is a potent β-lactam/β-lactamase inhibitor antibiotic commonly prescribed in the intensive care unit setting. Admitted patients often show large variability in treatment response due to multiple pathophysiological changes present in this population that alter the drug’s pharmacokinetics. This review summarizes the population pharmacokinetic models developed for piperacillin-tazobactam and provides comprehensive data on current dosing strategies while identifying significant covariates in critically ill patients. A literature search on the PubMed database was conducted, from its inception to July 2020. Relevant articles were retained if they met the defined inclusion/exclusion criteria. A total of ten studies, published between 2009 and 2020, were eligible. One- and two-compartment models were used in two and eight studies, respectively. The lowest estimated piperacillin clearance value was 3.12 L/h, and the highest value was 19.9 L/h. The estimations for volume of distribution varied between 11.2 and 41.2 L. Tazobactam clearance values ranged between 5.1 and 6.78 L/h, and tazobactam volume of distribution values ranged between 17.5 and 76.1 L. The most frequent covariates were creatinine clearance and body weight, each present in four studies. Almost all studies used an exponential approach for the interindividual variability. The highest variability was observed in piperacillin central volume of distribution, at a value of 75.0%. Simulations showed that continuous or extended infusion methods performed better than intermittent administration to achieve appropriate pharmacodynamic targets. This review synthesizes important pharmacokinetic elements for piperacillin-tazobactam in an intensive care unit setting. This will help clinicians better understand changes in the drug’s pharmacokinetic parameters in this specific population.

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Authors and Affiliations

  1. Faculty of Pharmacy, Université de Montréal, Pavillon Jean-Coutu, 2940 Chemin de Polytechnique, Montreal, QC, H3T 1J4, Canada

    Ibrahim El-Haffaf, Jean-Alexandre Caissy & Amélie Marsot

  2. Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada

    Ibrahim El-Haffaf, Jean-Alexandre Caissy & Amélie Marsot

  3. Centre de recherche, CHU Sainte-Justine, Montréal, QC, Canada

    Amélie Marsot

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Corresponding author

Correspondence to Ibrahim El-Haffaf.

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Funding

No sources of funding were used to assist in the preparation of this review.

Conflict of Interest

Ibrahim El-Haffaf received a scholarship from Université de Montréal. Amélie Marsot acknowledges support from the Fonds de Recherche du Québec-Santé (FRQS) Research Scholars – Junior 1 (Young Researcher Establishment) Career Scholarship and the Fonds Servier – Faculty of Pharmacy, Université de Montréal. Jean-Alexandre Caissy has no conflicts of interest to declare.

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Availability of data and material

Data was collected from the already published articles in the literature. Data generated to realize the various graphical analysis are not publicly available.

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Author’s contributions

IE analyzed the data. IE wrote the manuscript. JC and AM validated the manuscript. AM supervised the work. All authors read and approved the final manuscript.

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El-Haffaf, I., Caissy, JA. & Marsot, A. Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses. Clin Pharmacokinet 60, 855–875 (2021). https://doi.org/10.1007/s40262-021-01013-1

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  • DOI: https://doi.org/10.1007/s40262-021-01013-1

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