التفاصيل البيبلوغرافية
| العنوان: |
Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation. |
| المؤلفون: |
Jullien, Vincent, Azoulay, Elie, Schwebel, Carole, Le Saux, Thomas, Charles, Pierre Emmanuel, Cornet, Muriel, Souweine, Bertrand, Klouche, Kadda, Jaber, Samir, Trouillet, Jean-Louis, Bruneel, Fabrice, Cour, Martin, Cousson, Joel, Meziani, Ferhat, Gruson, Didier, Paris, Adeline, Darmon, Michael, Garrouste-Orgeas, Maité, Navellou, Jean-Christophe, Foucrier, Arnaud |
| المصدر: |
Journal of Antimicrobial Chemotherapy (JAC); Jan2017, Vol. 72 Issue 1, p181-189, 9p |
| مصطلحات موضوعية: |
SEPSIS, ARTIFICIAL respiration, PHARMACOKINETICS, ALBUMINS, CANDIDA albicans, ALLOMETRIC equations, ANTIFUNGAL agents, CANDIDA, COMPARATIVE studies, INTENSIVE care units, RESEARCH methodology, MEDICAL cooperation, MICROBIAL sensitivity tests, PEPTIDES, RESEARCH, SYSTEM analysis, EVALUATION research, CANDIDEMIA, PHARMACODYNAMICS |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
