Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime

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.