TY - JOUR
T1 - Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime
AU - Liu, Jiajun
AU - Neely, Michael
AU - Lipman, Jeffrey
AU - Sime, Fekade
AU - Roberts, Jason A.
AU - Kiel, Patrick J.
AU - Avedissian, Sean N.
AU - Rhodes, Nathaniel J.
AU - Scheetz, Marc H.
N1 - Funding Information:
J.A. Roberts would like to acknowledge funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452) and a Practitioner Fellowship (APP1117065).
Funding Information:
J.A. Roberts would like to acknowledge funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452) and a Practitioner Fellowship (APP1117065).
Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s40262-020-00873-3
DO - 10.1007/s40262-020-00873-3
M3 - Article
C2 - 32140940
AN - SCOPUS:85081580059
VL - 59
SP - 1027
EP - 1036
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
SN - 0312-5963
IS - 8
ER -