Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients

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  • dc.contributor.author Maseda, Emilio
  • dc.contributor.author Grau Cerrato, Santiago
  • dc.contributor.author Luque Pardos, Sònia
  • dc.contributor.author Castillo-Mafla, Maria-Pilar
  • dc.contributor.author Suárez-de-la-Rica, Alejandro
  • dc.contributor.author Montero-Feijoo, Ana
  • dc.contributor.author Salgado, Patricia
  • dc.contributor.author Giménez, Maria-José
  • dc.contributor.author García-Bernedo, Carlos A.
  • dc.contributor.author Gilsanz, Fernando
  • dc.contributor.author Roberts, Jason A.
  • dc.date.accessioned 2019-03-29T08:30:07Z
  • dc.date.available 2019-03-29T08:30:07Z
  • dc.date.issued 2018
  • dc.description.abstract BACKGROUND: Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC0-24h)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. METHODS: Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100-150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC0-24/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. RESULTS: Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg. CONCLUSION: The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Maseda E, Grau S, Luque S, Castillo-Mafla MP, Suárez-de-la-Rica A, Montero-Feijoo A. et al. Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients. Crit Care. 2018 Apr 15;22(1):94. DOI: 10.1186/s13054-018-2019-8
  • dc.identifier.doi http://dx.doi.org/10.1186/s13054-018-2019-8
  • dc.identifier.issn 1364-8535
  • dc.identifier.uri http://hdl.handle.net/10230/37008
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Critical Care. 2018 Apr 15;22(1):94
  • dc.rights Copyright © The Author(s). 2018. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Candida spp
  • dc.subject.keyword Intensive care unit
  • dc.subject.keyword Monte-Carlo simulation
  • dc.subject.keyword Morbid obesity
  • dc.subject.keyword PK/PD
  • dc.subject.other Obesitat
  • dc.title Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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