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Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation

Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients w...

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Autores principales: Alqahtani, Saeed, Alfarhan, Asma, Alsultan, Abdullah, Alsarhani, Emad, Alsubaie, Abdulaziz, Asiri, Yousif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615109/
https://www.ncbi.nlm.nih.gov/pubmed/34827301
http://dx.doi.org/10.3390/antibiotics10111363
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author Alqahtani, Saeed
Alfarhan, Asma
Alsultan, Abdullah
Alsarhani, Emad
Alsubaie, Abdulaziz
Asiri, Yousif
author_facet Alqahtani, Saeed
Alfarhan, Asma
Alsultan, Abdullah
Alsarhani, Emad
Alsubaie, Abdulaziz
Asiri, Yousif
author_sort Alqahtani, Saeed
collection PubMed
description Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography. Pharmacokinetic parameters were estimated using Monolix 4.4 software. The plasma micafungin concentrations were measured in a total of 133 samples from 19 patients. In the final two-compartment model with linear elimination, the estimated micafungin clearance (CL) was significantly higher in patients with cancer than in those without cancer (1.2 vs. 0.6 L/h, p = 0.012), whereas other parameters did not significantly differ between the two groups. Aspartate and alanine transaminases and body weight significantly influenced micafungin CL in patients, with and without cancer. Overall, the probability of target attainment increased with increasing doses and decreased with higher MICs in both groups. In simulations, the patients without cancer achieved higher pharmacokinetic/pharmacodynamic targets with a 90% probability for all simulated doses, compared to the patients with cancer. Micafungin demonstrated dose-proportional linear pharmacokinetics in both the patients with and those without cancer. The estimated micafungin CL was significantly higher in patients with cancer, suggesting a need for increased dosage, especially for Candida spp. with high MICs, in these patients. Further studies should assess the efficacy and optimum dosage of micafungin for the treatment and prevention of febrile neutropenia (FN) in patients with cancer.
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spelling pubmed-86151092021-11-26 Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation Alqahtani, Saeed Alfarhan, Asma Alsultan, Abdullah Alsarhani, Emad Alsubaie, Abdulaziz Asiri, Yousif Antibiotics (Basel) Article Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography. Pharmacokinetic parameters were estimated using Monolix 4.4 software. The plasma micafungin concentrations were measured in a total of 133 samples from 19 patients. In the final two-compartment model with linear elimination, the estimated micafungin clearance (CL) was significantly higher in patients with cancer than in those without cancer (1.2 vs. 0.6 L/h, p = 0.012), whereas other parameters did not significantly differ between the two groups. Aspartate and alanine transaminases and body weight significantly influenced micafungin CL in patients, with and without cancer. Overall, the probability of target attainment increased with increasing doses and decreased with higher MICs in both groups. In simulations, the patients without cancer achieved higher pharmacokinetic/pharmacodynamic targets with a 90% probability for all simulated doses, compared to the patients with cancer. Micafungin demonstrated dose-proportional linear pharmacokinetics in both the patients with and those without cancer. The estimated micafungin CL was significantly higher in patients with cancer, suggesting a need for increased dosage, especially for Candida spp. with high MICs, in these patients. Further studies should assess the efficacy and optimum dosage of micafungin for the treatment and prevention of febrile neutropenia (FN) in patients with cancer. MDPI 2021-11-08 /pmc/articles/PMC8615109/ /pubmed/34827301 http://dx.doi.org/10.3390/antibiotics10111363 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alqahtani, Saeed
Alfarhan, Asma
Alsultan, Abdullah
Alsarhani, Emad
Alsubaie, Abdulaziz
Asiri, Yousif
Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
title Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
title_full Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
title_fullStr Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
title_full_unstemmed Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
title_short Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
title_sort assessment of micafungin dosage regimens in patients with cancer using pharmacokinetic/pharmacodynamic modeling and monte carlo simulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615109/
https://www.ncbi.nlm.nih.gov/pubmed/34827301
http://dx.doi.org/10.3390/antibiotics10111363
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