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14-06-2022 | Linezolid | Review Article

A Review of Population Pharmacokinetic Analyses of Linezolid

Authors: Enrique Bandín-Vilar, Laura García-Quintanilla, Ana Castro-Balado, Irene Zarra-Ferro, Miguel González-Barcia, Manuel Campos-Toimil, Víctor Mangas-Sanjuan, Cristina Mondelo-García, Anxo Fernández-Ferreiro

Published in: Clinical Pharmacokinetics | Issue 6/2022

Abstract

In recent years, many studies on population pharmacokinetics of linezolid have been conducted. This comprehensive review aimed to summarize population pharmacokinetic models of linezolid, by focusing on dosage optimization to maximize the probability of attaining a certain pharmacokinetic-pharmacodynamic parameter in special populations. We searched the PubMed and EMBASE databases for population pharmacokinetic analyses of linezolid using a parametric non-linear mixed-effect approach, including both observational and prospective trials. Of the 32 studies, 26 were performed in adults, four in children, and one in both adults and children. High between-subject variability was determined in the majority of the models, which was in line with the variability of linezolid concentrations previously detected in observational studies. Some studies found that patients with renal impairment, hepatic failure, advanced age, or low body weight had higher exposure and adverse reactions rates. In contrast, lower concentrations and therapeutic failure were associated with obese patients, young patients, and patients who had undergone renal replacement techniques. In critically ill patients, the inter-individual and intra-individual variability was even greater, suggesting that this population is at an even higher risk of underexposure and overexposure. Therapeutic drug monitoring may be warranted in a large proportion of patients given that the Monte Carlo simulations demonstrated that the one-size-fits-all labeled dosing of 600 mg every 12 h could lead to toxicity or therapeutic failure for high values of the minimum inhibitory concentration of the target pathogen. Further research on covariates, including renal function, hepatic function, and drug–drug interactions related to P-glycoprotein could help to explain variability and improve linezolid dosing regimens.

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Title: A Review of Population Pharmacokinetic Analyses of Linezolid
Authors: Enrique Bandín-Vilar
Laura García-Quintanilla
Ana Castro-Balado
Irene Zarra-Ferro
Miguel González-Barcia
Manuel Campos-Toimil
Víctor Mangas-Sanjuan
Cristina Mondelo-García
Anxo Fernández-Ferreiro
Publication date: 14-06-2022
Publisher: Springer International Publishing
Keyword: Linezolid
Published in: Clinical Pharmacokinetics / Issue 6/2022
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-022-01125-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A Review of Population Pharmacokinetic Analyses of Linezolid

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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