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Article Dans Une Revue Journal of Antimicrobial Chemotherapy Année : 2017

Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation

1 Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [CHU Pitié-Salpétriêre]
2 AP-HP - Hopital Saint-Louis [AP-HP]
3 Service de Réanimation Médicale [Grenoble]
4 Département de Chimie - ENS Paris
5 UPMC - Université Pierre et Marie Curie - Paris 6
6 Service de Réanimation Médicale (CHU de Dijon)
7 TIMC-IMAG-TheREx - Thérapeutique Recombinante Expérimentale
8 LMGE - Laboratoire Microorganismes : Génome et Environnement
9 Département d'anesthésie-réanimation[Montpellier]
10 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
13 Service de réanimation [CH Versailles]
14 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
15 Hôpital universitaire Robert Debré [Reims]
16 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
17 CHU Bordeaux
18 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
19 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
20 Epidémiologie pronostique des cancers et affections graves
21 Service de Réanimation médicale [CHRU Besançon]
22 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
23 Service de réanimation médicale
24 Irset - Institut de recherche en santé, environnement et travail
25 SSI - Space Science Institute [Boulder]
26 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
Elie Azoulay
Martin Cour
Didier Gruson
  • Fonction : Auteur

Résumé

Objectives: To identify the factors associated with the interindividual pharmacokinetic (PK) variability of micafungin and to evaluate the probability of reaching the previously determined PK/pharmacodynamic efficacy thresholds (AUC/MIC >5000 for non-parapsilosis Candida sp. and ≥285 for Candida parapsilosis) with the recommended 100 mg daily dose in ICU patients with sepsis and mechanical ventilation.Methods: One hundred patients were included and 436 concentrations were available for PK analysis performed with NONMEM software. PTA was determined by Monte Carlo simulations.Results: Micafungin obeyed a two-compartment model with first-order elimination from the central compartment. Mean parameter estimates (percentage interindividual variability) were 1.34 L/h (34%) for clearance (CL), 11.80 L (38%) and 7.68 L (39%) for central (Vc) and peripheral (Vp) distribution volumes, respectively, and 4.67 L/h (37%) for distribution clearance. CL, Vc and Vp increased by 14% when the albumin level was ≤25 g/L and CL decreased by 25% when SOFA score was ≥10. Body weight was related to CL, Vc and Vp by allometric models. PTA was ≥90% in Candida albicans and Candida glabrata infections, except when the MIC was ≥0.015 mg/L, and ranged between 0% and 40% for C. parapsilosis infections with MIC ≥0.5 mg/L.Conclusions: A possible increase in the dose should be evaluated for infections due to C. parapsilosis and for infections due to C. albicans and C. glabrata with MICs ≥0.015 mg/L.
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Dates et versions

hal-01470808 , version 1 (08-04-2020)

Identifiants

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Vincent Jullien, Elie Azoulay, Carole Schwebel, Thomas Le Saux, Pierre Emmanuel Charles, et al.. Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation. Journal of Antimicrobial Chemotherapy, 2017, 72 (1), pp.181 - 189. ⟨10.1093/jac/dkw352⟩. ⟨hal-01470808⟩
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