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...

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Autores principales:	Abigail Ferreira, Helena Martins, José Carlos Oliveira, Rui Lapa, Nuno Vale
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PBPK modeling therapeutic drug monitoring antibiotics use amikacin gentamicin tobramycin Science Q
Acceso en línea:	https://doaj.org/article/4684e97e9bae46baaf3c3f14c007bd74
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spelling	oai:doaj.org-article:4684e97e9bae46baaf3c3f14c007bd742021-11-25T18:10:31ZPBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice10.3390/life111111302075-1729https://doaj.org/article/4684e97e9bae46baaf3c3f14c007bd742021-10-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1130https://doaj.org/toc/2075-1729The 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.Abigail FerreiraHelena MartinsJosé Carlos OliveiraRui LapaNuno ValeMDPI AGarticlePBPK modelingtherapeutic drug monitoringantibiotics useamikacingentamicintobramycinScienceQENLife, Vol 11, Iss 1130, p 1130 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PBPK modeling therapeutic drug monitoring antibiotics use amikacin gentamicin tobramycin Science Q
spellingShingle	PBPK modeling therapeutic drug monitoring antibiotics use amikacin gentamicin tobramycin Science Q Abigail Ferreira Helena Martins José Carlos Oliveira Rui Lapa Nuno Vale PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice
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	article
author	Abigail Ferreira Helena Martins José Carlos Oliveira Rui Lapa Nuno Vale
author_facet	Abigail Ferreira Helena Martins José Carlos Oliveira Rui Lapa Nuno Vale
author_sort	Abigail Ferreira
title	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_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_sort	pbpk modeling and simulation of antibiotics amikacin, gentamicin, tobramycin, and vancomycin used in hospital practice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4684e97e9bae46baaf3c3f14c007bd74
work_keys_str_mv	AT abigailferreira pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice AT helenamartins pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice AT josecarlosoliveira pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice AT ruilapa pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice AT nunovale pbpkmodelingandsimulationofantibioticsamikacingentamicintobramycinandvancomycinusedinhospitalpractice
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PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice

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