Population pharmacokinetics of daptomycin in critically ill patients

Daptomycin has shown activity against a wide range of Gram-positive bacteria; however, the approved dosages usually seem insufficient for critically ill patients. The aim of this study was to develop a population pharmacokinetic model for daptomycin in critically ill patients and to estimate the suc...

Descripción completa

Detalles Bibliográficos
Autores: Soraluce Olañeta, Amaia, Asín-Prieto, Eduardo, Rodríguez Gascón, Alicia, Barrasa González, Helena, Maynar, Javier, Carcelero, Esther, Soy, Dolors, Isla Ruiz, Arantxazu
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/64185
Acceso en línea:http://hdl.handle.net/10810/64185
Access Level:acceso abierto
Palabra clave:continuous renal replacement therapies
critically ill
daptomycin
pharmacokinetic/pharmacodynamic analysis
pharmacokinetics
id ES_58ffb00a5411f7982216ea2250b0187f
oai_identifier_str oai:addi.ehu.eus:10810/64185
network_acronym_str ES
network_name_str España
repository_id_str
spelling Population pharmacokinetics of daptomycin in critically ill patientsSoraluce Olañeta, AmaiaAsín-Prieto, EduardoRodríguez Gascón, AliciaBarrasa González, HelenaMaynar, JavierCarcelero, EstherSoy, DolorsIsla Ruiz, Arantxazucontinuous renal replacement therapiescritically illdaptomycinpharmacokinetic/pharmacodynamic analysispharmacokineticsDaptomycin has shown activity against a wide range of Gram-positive bacteria; however, the approved dosages usually seem insufficient for critically ill patients. The aim of this study was to develop a population pharmacokinetic model for daptomycin in critically ill patients and to estimate the success of the therapy by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. Sixteen intensive care unit patients were included, four of whom underwent continuous renal replacement therapies (CRRT). Blood and, when necessary, effluent samples were drawn after daptomycin administration at previously defined time points. A population approach using NONMEM 7.3 was performed to analyse data. Monte Carlo simulations were executed to evaluate the suitability of different dosage regimens. The probabilities of achieving the PK/PD target value associated with treatment success (ratio of the area under the plasma concentration-time curve over 24 h divided by the minimum inhibitory concentration (AUC24/MIC ≥ 666)) and to reach daptomycin concentrations linked to toxicity (minimum concentration at steady-state (Cminss) ≥ 24.3 mg/L) were calculated. The pharmacokinetics of daptomycin was best described by a one-compartment model. Elimination was conditioned by the creatinine clearance (Clcr) and also by the extra-corporeal clearance when patients were subjected to continuous renal replacement therapy (CRRT). The PK/PD analysis confirmed that 280- and 420-mg/d dosages would not be enough to achieve high probabilities of target attainment for MIC values ≥ 1 mg/L in patients with Clcr ≥ 60 mL/min or in subjects with lower Clcrs but receiving CRRT. In these patients, higher dosages (560-840 mg/d) should be needed. When treating infections due to MIC values ≥ 4 mg/L, even the highest dose would be insufficient.This study was supported by the University of the Basque Country UPV/EHU (PPG17/65).Elsevier202420242018info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/64185reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.sciencedirect.com/science/article/pii/S0924857918300797info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/© 2018 Elsevier B.V. and International Society of Chemotherapy under CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)oai:addi.ehu.eus:10810/641852026-06-18T09:23:17Z
dc.title.none.fl_str_mv Population pharmacokinetics of daptomycin in critically ill patients
title Population pharmacokinetics of daptomycin in critically ill patients
spellingShingle Population pharmacokinetics of daptomycin in critically ill patients
Soraluce Olañeta, Amaia
continuous renal replacement therapies
critically ill
daptomycin
pharmacokinetic/pharmacodynamic analysis
pharmacokinetics
title_short Population pharmacokinetics of daptomycin in critically ill patients
title_full Population pharmacokinetics of daptomycin in critically ill patients
title_fullStr Population pharmacokinetics of daptomycin in critically ill patients
title_full_unstemmed Population pharmacokinetics of daptomycin in critically ill patients
title_sort Population pharmacokinetics of daptomycin in critically ill patients
dc.creator.none.fl_str_mv Soraluce Olañeta, Amaia
Asín-Prieto, Eduardo
Rodríguez Gascón, Alicia
Barrasa González, Helena
Maynar, Javier
Carcelero, Esther
Soy, Dolors
Isla Ruiz, Arantxazu
author Soraluce Olañeta, Amaia
author_facet Soraluce Olañeta, Amaia
Asín-Prieto, Eduardo
Rodríguez Gascón, Alicia
Barrasa González, Helena
Maynar, Javier
Carcelero, Esther
Soy, Dolors
Isla Ruiz, Arantxazu
author_role author
author2 Asín-Prieto, Eduardo
Rodríguez Gascón, Alicia
Barrasa González, Helena
Maynar, Javier
Carcelero, Esther
Soy, Dolors
Isla Ruiz, Arantxazu
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv continuous renal replacement therapies
critically ill
daptomycin
pharmacokinetic/pharmacodynamic analysis
pharmacokinetics
topic continuous renal replacement therapies
critically ill
daptomycin
pharmacokinetic/pharmacodynamic analysis
pharmacokinetics
description Daptomycin has shown activity against a wide range of Gram-positive bacteria; however, the approved dosages usually seem insufficient for critically ill patients. The aim of this study was to develop a population pharmacokinetic model for daptomycin in critically ill patients and to estimate the success of the therapy by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. Sixteen intensive care unit patients were included, four of whom underwent continuous renal replacement therapies (CRRT). Blood and, when necessary, effluent samples were drawn after daptomycin administration at previously defined time points. A population approach using NONMEM 7.3 was performed to analyse data. Monte Carlo simulations were executed to evaluate the suitability of different dosage regimens. The probabilities of achieving the PK/PD target value associated with treatment success (ratio of the area under the plasma concentration-time curve over 24 h divided by the minimum inhibitory concentration (AUC24/MIC ≥ 666)) and to reach daptomycin concentrations linked to toxicity (minimum concentration at steady-state (Cminss) ≥ 24.3 mg/L) were calculated. The pharmacokinetics of daptomycin was best described by a one-compartment model. Elimination was conditioned by the creatinine clearance (Clcr) and also by the extra-corporeal clearance when patients were subjected to continuous renal replacement therapy (CRRT). The PK/PD analysis confirmed that 280- and 420-mg/d dosages would not be enough to achieve high probabilities of target attainment for MIC values ≥ 1 mg/L in patients with Clcr ≥ 60 mL/min or in subjects with lower Clcrs but receiving CRRT. In these patients, higher dosages (560-840 mg/d) should be needed. When treating infections due to MIC values ≥ 4 mg/L, even the highest dose would be insufficient.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/64185
url http://hdl.handle.net/10810/64185
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S0924857918300797
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869408583080214528
score 15,301603

Similares en LA Referencia