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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Saeed Alqahtani, Asma Alfarhan, Abdullah Alsultan, Emad Alsarhani, Abdulaziz Alsubaie, Yousif Asiri
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	micafungin cancer population pharmacokinetics modeling Monte Carlo simulation Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/618a67d66f8840e8af1f6655b2a58439
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:618a67d66f8840e8af1f6655b2a58439
record_format	dspace
spelling	oai:doaj.org-article:618a67d66f8840e8af1f6655b2a584392021-11-25T16:23:42ZAssessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation10.3390/antibiotics101113632079-6382https://doaj.org/article/618a67d66f8840e8af1f6655b2a584392021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1363https://doaj.org/toc/2079-6382Micafungin 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, <i>p</i> = 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 <i>Candida</i> 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.Saeed AlqahtaniAsma AlfarhanAbdullah AlsultanEmad AlsarhaniAbdulaziz AlsubaieYousif AsiriMDPI AGarticlemicafungincancerpopulation pharmacokineticsmodelingMonte Carlo simulationTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1363, p 1363 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	micafungin cancer population pharmacokinetics modeling Monte Carlo simulation Therapeutics. Pharmacology RM1-950
spellingShingle	micafungin cancer population pharmacokinetics modeling Monte Carlo simulation Therapeutics. Pharmacology RM1-950 Saeed Alqahtani Asma Alfarhan Abdullah Alsultan Emad Alsarhani Abdulaziz Alsubaie Yousif Asiri Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation
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, <i>p</i> = 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 <i>Candida</i> 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.
format	article
author	Saeed Alqahtani Asma Alfarhan Abdullah Alsultan Emad Alsarhani Abdulaziz Alsubaie Yousif Asiri
author_facet	Saeed Alqahtani Asma Alfarhan Abdullah Alsultan Emad Alsarhani Abdulaziz Alsubaie Yousif Asiri
author_sort	Saeed Alqahtani
title	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_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_sort	assessment of micafungin dosage regimens in patients with cancer using pharmacokinetic/pharmacodynamic modeling and monte carlo simulation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/618a67d66f8840e8af1f6655b2a58439
work_keys_str_mv	AT saeedalqahtani assessmentofmicafungindosageregimensinpatientswithcancerusingpharmacokineticpharmacodynamicmodelingandmontecarlosimulation AT asmaalfarhan assessmentofmicafungindosageregimensinpatientswithcancerusingpharmacokineticpharmacodynamicmodelingandmontecarlosimulation AT abdullahalsultan assessmentofmicafungindosageregimensinpatientswithcancerusingpharmacokineticpharmacodynamicmodelingandmontecarlosimulation AT emadalsarhani assessmentofmicafungindosageregimensinpatientswithcancerusingpharmacokineticpharmacodynamicmodelingandmontecarlosimulation AT abdulazizalsubaie assessmentofmicafungindosageregimensinpatientswithcancerusingpharmacokineticpharmacodynamicmodelingandmontecarlosimulation AT yousifasiri assessmentofmicafungindosageregimensinpatientswithcancerusingpharmacokineticpharmacodynamicmodelingandmontecarlosimulation
_version_	1718413202599968768

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

Ejemplares similares