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Population pharmacokinetics and pharmacodynamics of imipenem in neutropenic adult patients.
- Source :
-
Infectious diseases now [Infect Dis Now] 2023 Feb; Vol. 53 (1), pp. 104625. Date of Electronic Publication: 2022 Sep 27. - Publication Year :
- 2023
-
Abstract
- Objective: Imipenem is recommended in patients with chemotherapy-induced febrile neutropenia. Although alterations of antibiotic pharmacokinetic parameters have been reported in such patients, little data is available on imipenem.<br />Methods: Prospective, single-center, non-interventional pharmacokinetic cohort study in adults with chemotherapy-induced febrile neutropenia. Critically ill patients were excluded. Imipenem was administered as a 30-min infusion of 1000 mg/8h. Total imipenem plasma concentrations were assayed by high-performance liquid chromatography during neutropenia and just after neutrophil recovery. We estimated population pharmacokinetic parameters of imipenem by non-linear mixed-effect modelling using the SAEM algorithm.<br />Results: Sixteen patients were included in the study, including nine women (56.3%), median age 37 years (range, 18.3; 78.3). Eight patients had an hematological malignancy (50.0%) and seven had a solid tumor (43.8%). Imipenem pharmacokinetics were best described by a one-compartment model with first-order elimination. Mean values for imipenem were: clearance 14.3L/h and 10.9L/h and volume of distribution 20.7L and 14.5 L during neutropenia and after recovery, respectively. Imipenem plasma area under the curve at steady state was reduced by 23% during neutropenia. However, all patients achieved a pharmacodynamic target of %fT <subscript>>MIC</subscript>  ≥ 40% with a regimen of 1000 mg/8 h or 500 mg/6 h, for MICs up to 2 mg/L. The pharmacodynamics profile for a target of %fT > MIC = 100% was however less favorable with 500 mg/6 h or 1000 mg/8 h either during or after neutropenia.<br />Conclusion: Pharmacokinetic/pharmacodynamic goals for imipenem were similar in patients during and after neutropenia, despite reduced plasma exposure.<br /> (Copyright © 2022. Published by Elsevier Masson SAS.)
Details
- Language :
- English
- ISSN :
- 2666-9919
- Volume :
- 53
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Infectious diseases now
- Publication Type :
- Academic Journal
- Accession number :
- 36174960
- Full Text :
- https://doi.org/10.1016/j.idnow.2022.09.020