4.4 Review

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

Journal

CLINICAL PHARMACOKINETICS
Volume 60, Issue 7, Pages 855-875

Publisher

ADIS INT LTD
DOI: 10.1007/s40262-021-01013-1

Keywords

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Funding

  1. Universite de Montreal
  2. Fonds de Recherche du Quebec-Sante (FRQS) Research Scholars -Junior 1 (Young Researcher Establishment) Career Scholarship
  3. Fonds Servier -Faculty of Pharmacy, Universite de Montreal

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This review summarizes population pharmacokinetic models for Piperacillin-tazobactam in the intensive care unit, providing comprehensive data on dosing strategies and identifying significant covariates in critically ill patients. Studies showed variability in drug clearance and volume of distribution, with creatinine clearance and body weight being common covariates. Continuous or extended infusion methods were found to be more effective than intermittent administration in achieving appropriate pharmacodynamic targets.
Piperacillin-tazobactam is a potent beta-lactam/beta-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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