ArticleInternational journal of clinical pharmacy2025
Population pharmacokinetics of imipenem and target attainment of pharmacokinetic/pharmacodynamic indices in Chinese adults with febrile neutropenia and hematological malignancies.
Article in International journal of clinical pharmacy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Toward adaptive therapeutic timing: integration of mechanistic pharmacology and artificial intelligence in precision dosing.Frontiers in pharmacology · 2026Review
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Authors and funding
9 authors.
Funding
Abstract
introductionFebrile neutropenia (FN) in patients with hematological malignancies is associated with high morbidity and mortality due to bacterial infections, particularly from Gram-negative pathogens. Imipenem is widely used in this setting; however, altered pharmacokinetics in these patients may compromise treatment efficacy, necessitating individualized dosing strategies.
aimThis study aimed to develop a population pharmacokinetic model for imipenem in Chinese adult patients with FN and hematological malignancies and to identify optimal pharmacokinetic/pharmacodynamic (PK/PD) targets to guide dosing and predict antimicrobial efficacy.
methodA prospective, single-center, open-label study was conducted involving 121 hospitalized patients who contributed 207 plasma samples. Imipenem concentrations were measured by high-performance liquid chromatography. Pharmacokinetic modeling was performed using NONMEM, incorporating patient-specific covariates. Monte Carlo simulations were used to evaluate dosing regimens, and antimicrobial efficacy was assessed based on clinical and microbiological outcomes. The predictive value of PK/PD indices was analyzed using logistic regression and ROC curve analysis.
resultsA two-compartment model best described imipenem pharmacokinetics. Creatinine clearance (CLCR), gamma-glutamyltransferase (GGT), and vancomycin (VAN) co-administration significantly influenced imipenem clearance. The final model was: CL (L·h
conclusionThis study highlights the importance of individualized dosing in FN patients with hematological malignancies. CLCR, GGT, and VAN co-administration significantly affect imipenem pharmacokinetics. Achieving f%T > MIC of 90.48% is critical for efficacy. Additional agents may be needed for infections caused by highly resistant organisms such as Pseudomonas aeruginosa and Acinetobacter baumannii.
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