Population pharmacokinetics of piperacillin in nonobese, obese, and morbidly obese critically ill patients

Alobaid, Abdulaziz S., Wallis, Steven C., Jarrett, Paul, Starr, Therese, Stuart, Janine, Lassig-Smith, Melissa, Mejia, Jenny Lisette Ordóñez, Roberts, Michael S., Roger, Claire, Udy, Andrew A., Lipman, Jeffrey and Roberts, Jason A. (2017) Population pharmacokinetics of piperacillin in nonobese, obese, and morbidly obese critically ill patients. Antimicrobial Agents and Chemotherapy, 61 3: . doi:10.1128/AAC.01276-16


Author Alobaid, Abdulaziz S.
Wallis, Steven C.
Jarrett, Paul
Starr, Therese
Stuart, Janine
Lassig-Smith, Melissa
Mejia, Jenny Lisette Ordóñez
Roberts, Michael S.
Roger, Claire
Udy, Andrew A.
Lipman, Jeffrey
Roberts, Jason A.
Title Population pharmacokinetics of piperacillin in nonobese, obese, and morbidly obese critically ill patients
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 1098-6596
0066-4804
Publication date 2017-03-01
Sub-type Article (original research)
DOI 10.1128/AAC.01276-16
Open Access Status Not yet assessed
Volume 61
Issue 3
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2018
Language eng
Formatted abstract
The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h-1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h-1. A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.
Keyword Antibiotics
Creatinine clearance
Dosing
Morbid obesity
Pharmacodynamics
Pharmacokinetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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