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

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 (AUC)/minimum inhibitory concentratio...

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Autores: Maseda, Emilio|||0000-0003-2898-7073, Grau, Santiago|||0000-0002-8428-1836, Luque, Sonia|||0000-0002-3215-320X, Castillo-Mafla, Maria-Pilar, Suárez-de-la-Rica, Alejandro, Montero-Feijoo, Ana, Salgado, Patricia, Gimenez, Maria-Jose, García-Bernedo, Carlos A., Gilsanz, Fernando, Roberts, Jason A.
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:190781
Acceso en línea:https://ddd.uab.cat/record/190781
https://dx.doi.org/urn:doi:10.1186/s13054-018-2019-8
Access Level:acceso abierto
Palabra clave:Morbid obesity
PK/PD
Monte-Carlo simulation
Intensive care unit
Candida spp
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spelling Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patientsMaseda, Emilio|||0000-0003-2898-7073Grau, Santiago|||0000-0002-8428-1836Luque, Sonia|||0000-0002-3215-320XCastillo-Mafla, Maria-PilarSuárez-de-la-Rica, AlejandroMontero-Feijoo, AnaSalgado, PatriciaGimenez, Maria-JoseGarcía-Bernedo, Carlos A.Gilsanz, FernandoRoberts, Jason A.Morbid obesityPK/PDMonte-Carlo simulationIntensive care unitCandida sppDosing 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 (AUC)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. 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 AUC/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (non parapsilosis 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%. Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m 2 and 150 mg for morbidly obese patients with BMI > 45 kg/m 2 (except two noncritically ill obese patients with BMI ~ 35 kg/m 2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m 2 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. 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.Universitat Autònoma de Barcelona 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/190781https://dx.doi.org/urn:doi:10.1186/s13054-018-2019-8reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1907812026-06-06T12:50:31Z
dc.title.none.fl_str_mv Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
title Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
spellingShingle Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
Maseda, Emilio|||0000-0003-2898-7073
Morbid obesity
PK/PD
Monte-Carlo simulation
Intensive care unit
Candida spp
title_short Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
title_full Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
title_fullStr Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
title_full_unstemmed Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
title_sort Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
dc.creator.none.fl_str_mv Maseda, Emilio|||0000-0003-2898-7073
Grau, Santiago|||0000-0002-8428-1836
Luque, Sonia|||0000-0002-3215-320X
Castillo-Mafla, Maria-Pilar
Suárez-de-la-Rica, Alejandro
Montero-Feijoo, Ana
Salgado, Patricia
Gimenez, Maria-Jose
García-Bernedo, Carlos A.
Gilsanz, Fernando
Roberts, Jason A.
author Maseda, Emilio|||0000-0003-2898-7073
author_facet Maseda, Emilio|||0000-0003-2898-7073
Grau, Santiago|||0000-0002-8428-1836
Luque, Sonia|||0000-0002-3215-320X
Castillo-Mafla, Maria-Pilar
Suárez-de-la-Rica, Alejandro
Montero-Feijoo, Ana
Salgado, Patricia
Gimenez, Maria-Jose
García-Bernedo, Carlos A.
Gilsanz, Fernando
Roberts, Jason A.
author_role author
author2 Grau, Santiago|||0000-0002-8428-1836
Luque, Sonia|||0000-0002-3215-320X
Castillo-Mafla, Maria-Pilar
Suárez-de-la-Rica, Alejandro
Montero-Feijoo, Ana
Salgado, Patricia
Gimenez, Maria-Jose
García-Bernedo, Carlos A.
Gilsanz, Fernando
Roberts, Jason A.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Morbid obesity
PK/PD
Monte-Carlo simulation
Intensive care unit
Candida spp
topic Morbid obesity
PK/PD
Monte-Carlo simulation
Intensive care unit
Candida spp
description 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 (AUC)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. 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 AUC/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (non parapsilosis 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%. Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m 2 and 150 mg for morbidly obese patients with BMI > 45 kg/m 2 (except two noncritically ill obese patients with BMI ~ 35 kg/m 2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m 2 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. 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.
publishDate 2018
dc.date.none.fl_str_mv 2
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/190781
https://dx.doi.org/urn:doi:10.1186/s13054-018-2019-8
url https://ddd.uab.cat/record/190781
https://dx.doi.org/urn:doi:10.1186/s13054-018-2019-8
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
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