Journal article
Evaluation of Empirical Dosing Regimens for Meropenem in Intensive Care Unit Patients Using Population Pharmacokinetic Modeling and Target Attainment Analysis
Antimicrobial agents and chemotherapy, Vol.67(1), e01312-22
01/09/2023
DOI: 10.1128/aac.01312-22
PMCID: PMC9872596
PMID: 36622154
Abstract
In the present study, population pharmacokinetic (PK) analysis was performed based on meropenem data from a prospective study conducted in 114 critically ill patients with a wide range of renal functions and various disease conditions. The final model was a one-compartment model with linear elimination, with creatinine clearance and continuous renal replacement therapy affecting clearance, and total bodyweight impacting the volume of distribution. Our model is a valuable addition to the existing meropenem population PK models, and it could be particularly useful during implementation of a therapeutic drug monitoring program combined with Bayesian forecasting. Based on the final model developed, comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 16 different dosing regimens. Simulation results showed that 2 g administered every 8 h with 3-h prolonged infusion (PI) and 4 g/day by continuous infusion (CI) appear to be two empirical dosing regimens that are superior to many other regimens when both target attainment and potential toxicity are considered and renal function information is not available. Following a daily CI dose of 6 g or higher, more than 30% of the population with a creatinine clearance of <60 mL/min is predicted to have neurotoxicity. With the availability of institution- and/or unit-specific meropenem susceptibility patterns, as well as an individual patient's renal function, our PTA results may represent useful references for physicians to make dosing decisions.
In the present study, population pharmacokinetic (PK) analysis was performed based on meropenem data from a prospective study conducted in 114 critically ill patients with a wide range of renal functions and various disease conditions. The final model was a one-compartment model with linear elimination, with creatinine clearance and continuous renal replacement therapy affecting clearance, and total bodyweight impacting the volume of distribution.
Details
- Title: Subtitle
- Evaluation of Empirical Dosing Regimens for Meropenem in Intensive Care Unit Patients Using Population Pharmacokinetic Modeling and Target Attainment Analysis
- Creators
- Guohua An - University of IowaC. Buddy Creech - Vanderbilt University Medical CenterNan Wu - University of IowaRoger L. Nation - Monash UniversityKenan Gu - National Institute of Allergy and Infectious DiseasesDemet Nalbant - University of IowaNatalia Jimenez-Truque - Vanderbilt University Medical CenterWilliam Fissell - Vanderbilt University Medical CenterStephanie Rolsma - Vanderbilt University Medical CenterPratish C. Patel - Vanderbilt University Medical CenterAmy Watanabe - EmmesNicholas Fishbane - EmmesCarl M. J. Kirkpatrick - Monash UniversityCornelia B. Landersdorfer - Monash UniversityPatricia Winokur - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.67(1), e01312-22
- Publisher
- Amer Soc Microbiology
- DOI
- 10.1128/aac.01312-22
- PMID
- 36622154
- PMCID
- PMC9872596
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Number of pages
- 14
- Grant note
- HHSN272200800008C / Division of Microbiology and Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, through Vaccine and Treatment Evaluation Unit University of Iowa VTEU study team
- Language
- English
- Date published
- 01/09/2023
- Academic Unit
- Infectious Diseases; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984366023602771
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