Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation

Limited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conduc...

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Autores principales:	Dong-Hwan Lee, Hyoung-Soo Kim, Sunghoon Park, Hwan-il Kim, Sun-Hee Lee, Yong-Kyun Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	meropenem population pharmacokinetics critically ill patient adult extracorporeal membrane oxygenation Monte Carlo simulation Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/8147efe6c5c14dfda55e26f5f711345d
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spelling	oai:doaj.org-article:8147efe6c5c14dfda55e26f5f711345d2021-11-25T18:41:15ZPopulation Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation10.3390/pharmaceutics131118611999-4923https://doaj.org/article/8147efe6c5c14dfda55e26f5f711345d2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1861https://doaj.org/toc/1999-4923Limited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conducted using non-linear mixed-effect modeling. Monte Carlo simulation was used to determine for how long the free drug concentration was above the minimum inhibitory concentration (MIC) at steady state conditions in patients with various degrees of renal function. Meropenem PK in critically ill patients was described using a two-compartment model, in which glomerular filtration rate was identified as a covariate for clearance. ECMO did not affect meropenem PK. The simulation results showed that the current meropenem dosing regimen would be sufficient for attaining 40%<i>f</i>T<sub>>MIC</sub> for <i>Pseudomonas aeruginosa</i> at MIC ≤ 4 mg/L. Prolonged infusion over 3 h or a high-dosage regimen of 2 g/8 h was needed for MIC > 2 mg/L or in patients with augmented renal clearance, for a target of 100%<i>f</i>T<sub>>MIC</sub> or 100%<i>f</i>T<sub>>4XMIC</sub>. Our study suggests that clinicians should consider prolonged infusion or a high-dosage regimen of meropenem, particularly when treating critically ill patients with augmented renal clearance or those infected with pathogens with decreased in vitro susceptibility, regardless of ECMO support.Dong-Hwan LeeHyoung-Soo KimSunghoon ParkHwan-il KimSun-Hee LeeYong-Kyun KimMDPI AGarticlemeropenempopulation pharmacokineticscritically ill patientadultextracorporeal membrane oxygenationMonte Carlo simulationPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1861, p 1861 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	meropenem population pharmacokinetics critically ill patient adult extracorporeal membrane oxygenation Monte Carlo simulation Pharmacy and materia medica RS1-441
spellingShingle	meropenem population pharmacokinetics critically ill patient adult extracorporeal membrane oxygenation Monte Carlo simulation Pharmacy and materia medica RS1-441 Dong-Hwan Lee Hyoung-Soo Kim Sunghoon Park Hwan-il Kim Sun-Hee Lee Yong-Kyun Kim Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
description	Limited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conducted using non-linear mixed-effect modeling. Monte Carlo simulation was used to determine for how long the free drug concentration was above the minimum inhibitory concentration (MIC) at steady state conditions in patients with various degrees of renal function. Meropenem PK in critically ill patients was described using a two-compartment model, in which glomerular filtration rate was identified as a covariate for clearance. ECMO did not affect meropenem PK. The simulation results showed that the current meropenem dosing regimen would be sufficient for attaining 40%<i>f</i>T<sub>>MIC</sub> for <i>Pseudomonas aeruginosa</i> at MIC ≤ 4 mg/L. Prolonged infusion over 3 h or a high-dosage regimen of 2 g/8 h was needed for MIC > 2 mg/L or in patients with augmented renal clearance, for a target of 100%<i>f</i>T<sub>>MIC</sub> or 100%<i>f</i>T<sub>>4XMIC</sub>. Our study suggests that clinicians should consider prolonged infusion or a high-dosage regimen of meropenem, particularly when treating critically ill patients with augmented renal clearance or those infected with pathogens with decreased in vitro susceptibility, regardless of ECMO support.
format	article
author	Dong-Hwan Lee Hyoung-Soo Kim Sunghoon Park Hwan-il Kim Sun-Hee Lee Yong-Kyun Kim
author_facet	Dong-Hwan Lee Hyoung-Soo Kim Sunghoon Park Hwan-il Kim Sun-Hee Lee Yong-Kyun Kim
author_sort	Dong-Hwan Lee
title	Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
title_short	Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
title_full	Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
title_fullStr	Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
title_full_unstemmed	Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
title_sort	population pharmacokinetics of meropenem in critically ill korean patients and effects of extracorporeal membrane oxygenation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8147efe6c5c14dfda55e26f5f711345d
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Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation

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