Cargando…

PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice

The importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use o...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferreira, Abigail, Martins, Helena, Oliveira, José Carlos, Lapa, Rui, Vale, Nuno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620954/
https://www.ncbi.nlm.nih.gov/pubmed/34833005
http://dx.doi.org/10.3390/life11111130
_version_ 1784605341203300352
author Ferreira, Abigail
Martins, Helena
Oliveira, José Carlos
Lapa, Rui
Vale, Nuno
author_facet Ferreira, Abigail
Martins, Helena
Oliveira, José Carlos
Lapa, Rui
Vale, Nuno
author_sort Ferreira, Abigail
collection PubMed
description The importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use of antibiotics is crucial to ensure treatment efficacy and prevent toxicity caused by overdosing, as well as to combat the prevalence and wide spread of resistant strains. Some antibiotics have been selected and reserved for the treatment of severe infections, including amikacin, gentamicin, tobramycin, and vancomycin. Critically ill patients often require long treatments, hospitalization, and require particular attention regarding TDM and dosing adjustments. As these antibiotics are eliminated by the kidneys, critical deterioration of renal function and toxic effects must be prevented. In this work, clinical data from a Portuguese cohort of 82 inpatients was analyzed and physiologically based pharmacokinetic (PBPK) modeling and simulation was used to study the influence of different therapeutic regimens and parameters as biological sex, body weight, and renal function on the biodistribution and pharmacokinetic (PK) profile of these four antibiotics. Renal function demonstrated the greatest impact on plasma concentration of these antibiotics, and vancomycin had the most considerable accumulation in plasma over time, particularly in patients with impaired renal function. Thus, through a PBPK study, it is possible to understand which pharmacokinetic parameters will have the greatest variation in a given population receiving antibiotic administrations in hospital context.
format Online
Article
Text
id pubmed-8620954
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86209542021-11-27 PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice Ferreira, Abigail Martins, Helena Oliveira, José Carlos Lapa, Rui Vale, Nuno Life (Basel) Article The importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use of antibiotics is crucial to ensure treatment efficacy and prevent toxicity caused by overdosing, as well as to combat the prevalence and wide spread of resistant strains. Some antibiotics have been selected and reserved for the treatment of severe infections, including amikacin, gentamicin, tobramycin, and vancomycin. Critically ill patients often require long treatments, hospitalization, and require particular attention regarding TDM and dosing adjustments. As these antibiotics are eliminated by the kidneys, critical deterioration of renal function and toxic effects must be prevented. In this work, clinical data from a Portuguese cohort of 82 inpatients was analyzed and physiologically based pharmacokinetic (PBPK) modeling and simulation was used to study the influence of different therapeutic regimens and parameters as biological sex, body weight, and renal function on the biodistribution and pharmacokinetic (PK) profile of these four antibiotics. Renal function demonstrated the greatest impact on plasma concentration of these antibiotics, and vancomycin had the most considerable accumulation in plasma over time, particularly in patients with impaired renal function. Thus, through a PBPK study, it is possible to understand which pharmacokinetic parameters will have the greatest variation in a given population receiving antibiotic administrations in hospital context. MDPI 2021-10-23 /pmc/articles/PMC8620954/ /pubmed/34833005 http://dx.doi.org/10.3390/life11111130 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
Ferreira, Abigail
Martins, Helena
Oliveira, José Carlos
Lapa, Rui
Vale, Nuno
PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
title PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
title_full PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
title_fullStr PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
title_full_unstemmed PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
title_short PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
title_sort pbpk modeling and simulation of antibiotics amikacin, gentamicin, tobramycin, and vancomycin used in hospital practice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620954/
https://www.ncbi.nlm.nih.gov/pubmed/34833005
http://dx.doi.org/10.3390/life11111130
work_keys_str_mv AT ferreiraabigail pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice
AT martinshelena pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice
AT oliveirajosecarlos pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice
AT laparui pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice
AT valenuno pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice