Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients

ObjectivesTo assess the pharmacokinetics and pharmacodynamics of imipenem in a retrospective cohort of hospitalized Chinese older patients.MethodsA population pharmacokinetic (PPK) model was constructed utilizing a nonlinear mixed-effects modeling approach. The final model underwent evaluation throu...

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Main Authors: Jing Wang, Qiu Fang, Xuemei Luo, Lu Jin, Huaijun Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1524272/full
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author Jing Wang
Qiu Fang
Xuemei Luo
Lu Jin
Huaijun Zhu
Huaijun Zhu
author_facet Jing Wang
Qiu Fang
Xuemei Luo
Lu Jin
Huaijun Zhu
Huaijun Zhu
author_sort Jing Wang
collection DOAJ
description ObjectivesTo assess the pharmacokinetics and pharmacodynamics of imipenem in a retrospective cohort of hospitalized Chinese older patients.MethodsA 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.ResultsA 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.ConclusionThe 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.
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spelling doaj-art-c962e6b9babe4a9eaa98525b00089a562025-08-20T03:12:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15242721524272Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patientsJing Wang0Qiu Fang1Xuemei Luo2Lu Jin3Huaijun Zhu4Huaijun Zhu5Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaObjectivesTo assess the pharmacokinetics and pharmacodynamics of imipenem in a retrospective cohort of hospitalized Chinese older patients.MethodsA 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.ResultsA 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2024.1524272/fullimipenempopulation pharmacokineticsdosing optimizationelderly patientsMonte Carlo
spellingShingle Jing Wang
Qiu Fang
Xuemei Luo
Lu Jin
Huaijun Zhu
Huaijun Zhu
Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
Frontiers in Pharmacology
imipenem
population pharmacokinetics
dosing optimization
elderly patients
Monte Carlo
title Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
title_full Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
title_fullStr Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
title_full_unstemmed Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
title_short Population pharmacokinetics and dosing optimization of imipenem in Chinese elderly patients
title_sort population pharmacokinetics and dosing optimization of imipenem in chinese elderly patients
topic imipenem
population pharmacokinetics
dosing optimization
elderly patients
Monte Carlo
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1524272/full
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