Abstract
OBJECTIVES: To assess the pharmacokinetics and pharmacodynamics of imipenem in a retrospective cohort of hospitalized Chinese older patients. METHODS: A population pharmacokinetic (PPK) model was constructed utilizing a nonlinear mixed-effects modeling approach. The final model underwent evaluation through bootstrap resampling and visual predictive checks. Additionally, a population pharmacokinetic and pharmacodynamic analysis was conducted employing Monte Carlo simulations to investigate the impact of commonly used dosing regimens (0.25 g every 6 h, 0.5 g every 6 h, 0.5 g every 8 h, 1 g every 6 h, 1 g every 8 h, and 1 g every 12 h) on the likelihood of achieving the target therapeutic outcomes. RESULTS: A total of 370 observations available from 142 patients were incorporated in the PPK model. A two-compartment PPK model with linear elimination best predicted the imipenem plasma concentrations, with the creatinine clearance as a significant covariate of clearance. Typical estimates for clearance, inter-compartmental clearance, central and peripheral volume were 13.1 L·h(-1), 11.9 L·h(-1), 11.7 L, 29.3 L, respectively. CONCLUSION: The pharmacokinetics of imipenem in elderly patients were effectively characterized by the established PPK model, which includes creatinine clearance as a key covariate. This research will enhance our understanding of imipenem elimination and support precision dosing in this patient demographic.