@article{3020699,
    title = "Comparative pharmacokinetics of the three echinocandins in ICU patients",
    author = "Mainas, E. and Apostolopoulou, O. and Siopi, M. and Apostolidi, S. and Neroutsos, E. and Mirfendereski, H. and Marchand, S. and Couet, W. and Dokoumetzidis, A. and Valsami, G. and Sambatakou, H. and Dimopoulos, G. and Meletiadis, J.",
    journal = "Journal of Antimicrobial Chemotherapy (JAC)",
    year = "2020",
    volume = "75",
    number = "10",
    pages = "2969-2976",
    publisher = "Oxford University Press",
    issn = "0305-7453, 1460-2091",
    doi = "10.1093/jac/dkaa265",
    keywords = "anidulafungin;  caspofungin;  liver enzyme;  micafungin;  anidulafungin;  antifungal agent;  echinocandin;  lipopeptide, aged;  antifungal therapy;  area under the curve;  Article;  body mass;  Candida albicans;  Candida parapsilosis;  clinical article;  comparative study;  controlled study;  correlational study;  demography;  disease severity;  drug clearance;  drug exposure;  female;  human;  intensive care unit;  loading drug dose;  male;  pharmacokinetic parameters;  prospective study;  Sequential Organ Failure Assessment Score;  surgical ward;  tertiary care center;  volume of distribution;  intensive care unit;  microbial sensitivity test, Anidulafungin;  Antifungal Agents;  Echinocandins;  Humans;  Intensive Care Units;  Lipopeptides;  Microbial Sensitivity Tests;  Prospective Studies",
    abstract = "Background: We conducted a prospective study in ICU patients of two tertiary hospitals in order to determine basic pharmacokinetic (PK) parameters, associated variation and target attainment rates for anidulafungin, micafungin and caspofungin. Methods: Serum samples from patients treated for 7 days with the standard doses of anidulafungin (N= 13), micafungin (N= 14) or caspofungin (N= 7) were analysed by validated chromatographic methods. PK parameters determined with non-compartmental analysis were correlated with demographic, laboratory and disease severity characteristics. The percentages of patients attaining drug exposures described in the summary of product characteristics (SmPC) documents and preclinical PK/PD targets for stasis were estimated. Results: The median (range) AUC24 was 101.46 (54.95-274.15)mg-h/L for anidulafungin, 79.35 (28.00- 149.30)mg-h/L for micafungin and 48.46 (19.44-103.69)mg-h/L for caspofungin. The interindividual variability of anidulafungin, micafungin and caspofungin AUC24 was 46%-58%, attributed mainly to variability in volume of distribution (V), clearance (CL) and in both V and CL, respectively. Significant correlations were found between anidulafungin AUC24 and BMI (rs =#0.670, P = 0.012) and liver enzymes (rs = 0.572-0.665, P = 0.013-0.041) and between caspofungin Cmin and transaminase levels (rs =#0.775 to #0.786, P = 0.036-0.041). Less than 50% of our patients attained the corresponding SmPC median AUC24s and none of the patients attained the PK/PD targets for Candida albicans and Candida parapsilosis. Conclusions: Anidulafungin exposure in ICU patients was comparable with that reported in non-ICU patients and in healthy volunteers. Micafungin exposure was comparable to that of other patients but-30% lower than that in healthy volunteers, whereas caspofungin exposure was rather low (-50% lower than in healthy volunteers). Larger interindividual variability (50%-60%) was recorded in ICU patients compared with other groups for all three echinocandins. © 2020 Oxford University Press. All rights reserved."
}