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Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients
The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449215/ https://www.ncbi.nlm.nih.gov/pubmed/32660990 http://dx.doi.org/10.1128/AAC.00905-20 |
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author | Märtson, Anne-Grete van der Elst, Kim C. M. Veringa, Anette Zijlstra, Jan G. Beishuizen, Albertus van der Werf, Tjip S. Kosterink, Jos G. W. Neely, Michael Alffenaar, Jan-Willem |
author_facet | Märtson, Anne-Grete van der Elst, Kim C. M. Veringa, Anette Zijlstra, Jan G. Beishuizen, Albertus van der Werf, Tjip S. Kosterink, Jos G. W. Neely, Michael Alffenaar, Jan-Willem |
author_sort | Märtson, Anne-Grete |
collection | PubMed |
description | The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions, measured on day 3 (±1) of treatment. Pmetrics was used for population pharmacokinetic modeling and probability of target attainment (PTA). A target 24-h area under the concentration-time curve (AUC) value of 98 mg·h/liter was used as an efficacy parameter. Secondarily, the AUC/MIC targets of 450, 865, and 1,185 were used to calculate PTAs for Candida glabrata, C. albicans, and C. parapsilosis, respectively. The final 2-compartment model included weight as a covariate on volume of distribution (V). The mean V of the central compartment was 7.71 (standard deviation [SD], 2.70) liters/kg of body weight, the mean elimination constant (K(e)) was 0.09 (SD, 0.04) h(−1), the rate constant for the caspofungin distribution from the central to the peripheral compartment was 0.44 (SD, 0.39) h(−1), and the rate constant for the caspofungin distribution from the peripheral to the central compartment was 0.46 (SD, 0.35) h(−1). A loading dose of 2 mg/kg on the first day, followed by 1.25 mg/kg as a maintenance dose, was chosen. With this dose, 98% of the patients were expected to reach the AUC target on the first day and 100% of the patients on the third day. The registered caspofungin dose might not be suitable for critically ill patients who were all overweight (≥120 kg), over 80% of median weight (78 kg), and around 25% of lower weight (≤50 kg). A weight-based dose regimen might be appropriate for achieving adequate exposure of caspofungin in intensive care unit patients. |
format | Online Article Text |
id | pubmed-7449215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-74492152020-09-09 Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients Märtson, Anne-Grete van der Elst, Kim C. M. Veringa, Anette Zijlstra, Jan G. Beishuizen, Albertus van der Werf, Tjip S. Kosterink, Jos G. W. Neely, Michael Alffenaar, Jan-Willem Antimicrob Agents Chemother Pharmacology The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions, measured on day 3 (±1) of treatment. Pmetrics was used for population pharmacokinetic modeling and probability of target attainment (PTA). A target 24-h area under the concentration-time curve (AUC) value of 98 mg·h/liter was used as an efficacy parameter. Secondarily, the AUC/MIC targets of 450, 865, and 1,185 were used to calculate PTAs for Candida glabrata, C. albicans, and C. parapsilosis, respectively. The final 2-compartment model included weight as a covariate on volume of distribution (V). The mean V of the central compartment was 7.71 (standard deviation [SD], 2.70) liters/kg of body weight, the mean elimination constant (K(e)) was 0.09 (SD, 0.04) h(−1), the rate constant for the caspofungin distribution from the central to the peripheral compartment was 0.44 (SD, 0.39) h(−1), and the rate constant for the caspofungin distribution from the peripheral to the central compartment was 0.46 (SD, 0.35) h(−1). A loading dose of 2 mg/kg on the first day, followed by 1.25 mg/kg as a maintenance dose, was chosen. With this dose, 98% of the patients were expected to reach the AUC target on the first day and 100% of the patients on the third day. The registered caspofungin dose might not be suitable for critically ill patients who were all overweight (≥120 kg), over 80% of median weight (78 kg), and around 25% of lower weight (≤50 kg). A weight-based dose regimen might be appropriate for achieving adequate exposure of caspofungin in intensive care unit patients. American Society for Microbiology 2020-08-20 /pmc/articles/PMC7449215/ /pubmed/32660990 http://dx.doi.org/10.1128/AAC.00905-20 Text en Copyright © 2020 Märtson et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Pharmacology Märtson, Anne-Grete van der Elst, Kim C. M. Veringa, Anette Zijlstra, Jan G. Beishuizen, Albertus van der Werf, Tjip S. Kosterink, Jos G. W. Neely, Michael Alffenaar, Jan-Willem Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients |
title | Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients |
title_full | Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients |
title_fullStr | Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients |
title_full_unstemmed | Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients |
title_short | Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients |
title_sort | caspofungin weight-based dosing supported by a population pharmacokinetic model in critically ill patients |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449215/ https://www.ncbi.nlm.nih.gov/pubmed/32660990 http://dx.doi.org/10.1128/AAC.00905-20 |
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