Population pharmacokinetics and pharmacodynamics of imipenem in neutropenic adult patients

被引:2
作者
Lafaurie, M. [1 ,9 ]
Burdet, C. [2 ,3 ]
Hammas, K. [2 ]
Goldwirt, L. [4 ]
Bercot, B. [3 ,6 ]
Sauvageon, H. [4 ,5 ]
Houze, P. [7 ]
Fourmont, M. [8 ]
Mentre, F. [2 ,3 ]
Molina, J. M. [1 ,5 ]
机构
[1] Hop St Louis, AP HP, Dept Malad Infectieuses & Trop, Lariboisiere, F-75010 Paris, France
[2] Hop Bichat Claude Bernard, AP HP, Dept Epidemiol, Biostat & Rech Clin, F-75018 Paris, France
[3] Univ Paris, IAME, INSERM, F-75018 Paris, France
[4] Hop St Louis, AP HP, Lab Pharmacol Biol, F-75010 Paris, France
[5] Univ Paris, INSERM, UMR S976, F-75006 Paris, France
[6] Hop St Louis, AP HP, Serv Bacteriol, F-75010 Paris, France
[7] Univ Paris, UTCBS, CNRS,UMR8258, INSERM,U1022, Paris, France
[8] Unite Adolescent & Jeunes Adultes, Hop St Louis, AP HP, Serv Hematol, F-75010 Paris, France
[9] Hop St Louis, Serv Malad Infectieuses & Trop, 1 Ave Claude, F-75010 Vellefaux, Paris, France
来源
INFECTIOUS DISEASES NOW | 2023年 / 53卷 / 01期
关键词
Neutropenia; Pharmacokinetics; Pharmacodynamics; Imipenem; MINIMUM INHIBITORY CONCENTRATION; BETA-LACTAM ANTIBIOTICS; FEBRILE; PARAMETERS;
D O I
10.1016/j.idnow.2022.09.020
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.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/8 h. 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.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 14.3 L/h and 10.9 L/h and volume of distribution 20.7 L 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>MIC & GE; 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.Conclusion: Pharmacokinetic/pharmacodynamic goals for imipenem were similar in patients during and after neutropenia, despite reduced plasma exposure.
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页数:6
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