Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime
- PDF / 1,837,324 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 53 Downloads / 142 Views
ORIGINAL RESEARCH ARTICLE
Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime Jiajun Liu1,2,3 · Michael Neely4 · Jeffrey Lipman5,6,11 · Fekade Sime5,7 · Jason A. Roberts5,6,7,11 · Patrick J. Kiel8 · Sean N. Avedissian9,10 · Nathaniel J. Rhodes1,2,3 · Marc H. Scheetz1,2,3
© Springer Nature Switzerland AG 2020
Abstract Background and Objective Understanding pharmacokinetic disposition of cefepime, a β-lactam antibiotic, is crucial for developing regimens to achieve optimal exposure and improved clinical outcomes. This study sought to develop and evaluate a unified population pharmacokinetic model in both pediatric and adult patients receiving cefepime treatment. Methods Multiple physiologically relevant models were fit to pediatric and adult subject data. To evaluate the final model performance, a withheld group of 12 pediatric patients and two separate adult populations were assessed. Results Seventy subjects with a total of 604 cefepime concentrations were included in this study. All adults (n = 34) on average weighed 82.7 kg and displayed a mean creatinine clearance of 106.7 mL/min. All pediatric subjects (n = 36) had mean weight and creatinine clearance of 16.0 kg and 195.6 mL/min, respectively. A covariate-adjusted two-compartment model described the observed concentrations well (population model R2, 87.0%; Bayesian model R2, 96.5%). In the evaluation subsets, the model performed similarly well (population R2, 84.0%; Bayesian R2, 90.2%). Conclusion The identified model serves well for population dosing and as a Bayesian prior for precision dosing.
1 Introduction Cefepime is a commonly utilized antibiotic for nosocomial infections. Rising resistance, manifesting as increased cefepime minimum inhibitory concentrations (MICs), Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40262-020-00873-3) contains supplementary material, which is available to authorized users. * Marc H. Scheetz [email protected] 1
Midwestern University Chicago College of Pharmacy, 555 31st Street, Downers Grove, IL 60515, USA
has led to more frequent clinical failures [1, 2]. To advise clinical outcomes according to MICs, the Clinical and Laboratory Standards Institute updated the susceptibility breakpoints and then created a category of susceptibledose dependent for MICs of 4 and 8 mg/L for Enterobacteriaceae spp. [3]. Achieving goal pharmacokinetic exposures to effectively treat these higher MICs can require a precision dosing approach.
7
Centre for Translational Anti‑Infective Pharmacodynamics, School of Pharmacy, University of Queensland, Brisbane, QLD, Australia
8
Indiana University Health, Indianapolis, IN, USA
9
Antiviral Pharmacology Laboratory, University of Nebraska, Medical Center (UNMC) Center for Drug Discovery, Omaha, NE, USA
2
Northwestern Memorial Hospital, Chicago, IL, USA
3
Pharmacometrics Center of Excellence, Midwestern University Chicago College of Pharmacy, Downers Grove, IL, USA
1
Data Loading...
