Population pharmacokinetics and pharmacodynamics of imipenem in neutropenic adult patients - 11/02/23
, C. Burdet b, c, 1, K. Hammas b, L. Goldwirt d, B. Berçot c, f, H. Sauvageon d, e, P. Houze g, M. Fourmont h, F. Mentré b, c, J.M. Molina a, eHighlights |
• | Imipenem pharmacokinetic parameters were modified during neutropenia. |
• | However, reduced imipenem plasma exposure did not translate into a reduced probability of pharmacokinetic target attainment for MICs below 4 mg/L. |
• | Estimated PK profiles of patients at steady state following an intravenous infusion of imipenem, 500 mg every 6 hours, were similar to those following an infusion of 1000 mg every 8 hours. |
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.
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.
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>MIC ≥ 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.
Le texte complet de cet article est disponible en PDF.Keywords : Neutropenia, Pharmacokinetics, Pharmacodynamics, Imipenem
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Vol 53 - N° 1
Article 104625- février 2023 Retour au numéro
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