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Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK
Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially e...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554458/ https://www.ncbi.nlm.nih.gov/pubmed/36249803 http://dx.doi.org/10.3389/fphar.2022.977372 |
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author | Zazo, Hinojal Lagarejos, Eduardo Prado-Velasco, Manuel Sánchez-Herrero, Sergio Serna, Jenifer Rueda-Ferreiro, Almudena Martín-Suárez, Ana Calvo, M. Victoria Pérez-Blanco, Jonás Samuel Lanao, José M. |
author_facet | Zazo, Hinojal Lagarejos, Eduardo Prado-Velasco, Manuel Sánchez-Herrero, Sergio Serna, Jenifer Rueda-Ferreiro, Almudena Martín-Suárez, Ana Calvo, M. Victoria Pérez-Blanco, Jonás Samuel Lanao, José M. |
author_sort | Zazo, Hinojal |
collection | PubMed |
description | Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria. The PBPK model developed consisted of 2 flow-limited tissues: kidney and other tissues. It has been implemented on a new tool called PhysPK, which allows structure reusability and evolution as predictive engine in Model-Informed Precision Dosing (MIPD). Retrospective pharmacokinetic information based on serum levels data from 47 neonates with gestational age between 32 and 39 weeks and younger than one-week postnatal age were used for model validation. The minimal PBPK model developed adequately described the gentamicin serum concentration-time profile with an average fold error nearly 1. Extended interval gentamicin dosing regimens (6 mg/kg q36h and 6 mg/kg q48h for term and preterm neonates, respectively) showed efficacy higher than 99% with toxicity lower than 10% through Monte Carlo simulation evaluations. The gentamicin minimal PBPK model developed in PhysPK from literature information, and validated in preterm and term neonates, presents adequate predictive performance and could be useful for MIPD strategies in neonates. |
format | Online Article Text |
id | pubmed-9554458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95544582022-10-13 Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK Zazo, Hinojal Lagarejos, Eduardo Prado-Velasco, Manuel Sánchez-Herrero, Sergio Serna, Jenifer Rueda-Ferreiro, Almudena Martín-Suárez, Ana Calvo, M. Victoria Pérez-Blanco, Jonás Samuel Lanao, José M. Front Pharmacol Pharmacology Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria. The PBPK model developed consisted of 2 flow-limited tissues: kidney and other tissues. It has been implemented on a new tool called PhysPK, which allows structure reusability and evolution as predictive engine in Model-Informed Precision Dosing (MIPD). Retrospective pharmacokinetic information based on serum levels data from 47 neonates with gestational age between 32 and 39 weeks and younger than one-week postnatal age were used for model validation. The minimal PBPK model developed adequately described the gentamicin serum concentration-time profile with an average fold error nearly 1. Extended interval gentamicin dosing regimens (6 mg/kg q36h and 6 mg/kg q48h for term and preterm neonates, respectively) showed efficacy higher than 99% with toxicity lower than 10% through Monte Carlo simulation evaluations. The gentamicin minimal PBPK model developed in PhysPK from literature information, and validated in preterm and term neonates, presents adequate predictive performance and could be useful for MIPD strategies in neonates. Frontiers Media S.A. 2022-09-28 /pmc/articles/PMC9554458/ /pubmed/36249803 http://dx.doi.org/10.3389/fphar.2022.977372 Text en Copyright © 2022 Zazo, Lagarejos, Prado-Velasco, Sánchez-Herrero, Serna, Rueda-Ferreiro, Martín-Suárez, Calvo, Pérez-Blanco and Lanao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Zazo, Hinojal Lagarejos, Eduardo Prado-Velasco, Manuel Sánchez-Herrero, Sergio Serna, Jenifer Rueda-Ferreiro, Almudena Martín-Suárez, Ana Calvo, M. Victoria Pérez-Blanco, Jonás Samuel Lanao, José M. Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK |
title | Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK |
title_full | Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK |
title_fullStr | Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK |
title_full_unstemmed | Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK |
title_short | Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK |
title_sort | physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using physpk |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554458/ https://www.ncbi.nlm.nih.gov/pubmed/36249803 http://dx.doi.org/10.3389/fphar.2022.977372 |
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