Cargando…
Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia
BACKGROUND: Therapeutic hypothermia (TH) is the treatment of choice for neonates diagnosed with perinatal asphyxia (PA). Dosing recommendations of various therapeutic agents including antimicrobials were not specifically available for the neonates undergoing TH. METHODS: A systematic search methodol...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411058/ https://www.ncbi.nlm.nih.gov/pubmed/34493833 http://dx.doi.org/10.1038/s41390-021-01714-0 |
_version_ | 1784775235776544768 |
---|---|
author | Matcha, Saikumar Raj, Elstin Anbu Mahadevan, Ramya Raju, Arun Prasath Rajesh, V Lewis, Leslie Edward Mallayasamy, Surulivelrajan |
author_facet | Matcha, Saikumar Raj, Elstin Anbu Mahadevan, Ramya Raju, Arun Prasath Rajesh, V Lewis, Leslie Edward Mallayasamy, Surulivelrajan |
author_sort | Matcha, Saikumar |
collection | PubMed |
description | BACKGROUND: Therapeutic hypothermia (TH) is the treatment of choice for neonates diagnosed with perinatal asphyxia (PA). Dosing recommendations of various therapeutic agents including antimicrobials were not specifically available for the neonates undergoing TH. METHODS: A systematic search methodology was used to identify pharmacokinetic (PK) studies of antimicrobials during TH. Antimicrobials with multiple PK studies were identified to create a generalizable PK model. Pharmacometric simulations were performed using the PUMAS software platform to reproduce the results of published studies. A suitable model that could reproduce the results of all other published studies was identified. With the help of a generalizable model, an optimal dosage regimen was designed considering the important covariates of the identified model. RESULTS: With the systematic search, only gentamicin had multiple PK reports during TH. A generalizable model was identified and the model predictions could match the reported/observed concentrations of publications. Birth weight and serum creatinine were the significant covariates influencing the PK of gentamicin in neonates. A dosage nomogram was designed using pharmacometric simulations to maintain gentamicin concentrations below 10 μg/mL at peak and below 2 μg/mL at trough. CONCLUSIONS: A generalizable PK model for gentamicin during TH in neonates was identified. Using the model, a dosing nomogram for gentamicin was designed. IMPACT: Dosing guidelines for antimicrobials during TH in neonates is lacking. This is the first study to identify the generalizable model for gentamicin during TH in neonates. Nomogram, proposed in the study, will aid the clinicians to individualize gentamicin dosing regimen for neonates considering the birth weight and serum creatinine. |
format | Online Article Text |
id | pubmed-9411058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-94110582022-08-27 Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia Matcha, Saikumar Raj, Elstin Anbu Mahadevan, Ramya Raju, Arun Prasath Rajesh, V Lewis, Leslie Edward Mallayasamy, Surulivelrajan Pediatr Res Clinical Research Article BACKGROUND: Therapeutic hypothermia (TH) is the treatment of choice for neonates diagnosed with perinatal asphyxia (PA). Dosing recommendations of various therapeutic agents including antimicrobials were not specifically available for the neonates undergoing TH. METHODS: A systematic search methodology was used to identify pharmacokinetic (PK) studies of antimicrobials during TH. Antimicrobials with multiple PK studies were identified to create a generalizable PK model. Pharmacometric simulations were performed using the PUMAS software platform to reproduce the results of published studies. A suitable model that could reproduce the results of all other published studies was identified. With the help of a generalizable model, an optimal dosage regimen was designed considering the important covariates of the identified model. RESULTS: With the systematic search, only gentamicin had multiple PK reports during TH. A generalizable model was identified and the model predictions could match the reported/observed concentrations of publications. Birth weight and serum creatinine were the significant covariates influencing the PK of gentamicin in neonates. A dosage nomogram was designed using pharmacometric simulations to maintain gentamicin concentrations below 10 μg/mL at peak and below 2 μg/mL at trough. CONCLUSIONS: A generalizable PK model for gentamicin during TH in neonates was identified. Using the model, a dosing nomogram for gentamicin was designed. IMPACT: Dosing guidelines for antimicrobials during TH in neonates is lacking. This is the first study to identify the generalizable model for gentamicin during TH in neonates. Nomogram, proposed in the study, will aid the clinicians to individualize gentamicin dosing regimen for neonates considering the birth weight and serum creatinine. Nature Publishing Group US 2021-09-07 2022 /pmc/articles/PMC9411058/ /pubmed/34493833 http://dx.doi.org/10.1038/s41390-021-01714-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Research Article Matcha, Saikumar Raj, Elstin Anbu Mahadevan, Ramya Raju, Arun Prasath Rajesh, V Lewis, Leslie Edward Mallayasamy, Surulivelrajan Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
title | Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
title_full | Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
title_fullStr | Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
title_full_unstemmed | Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
title_short | Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
title_sort | pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia |
topic | Clinical Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411058/ https://www.ncbi.nlm.nih.gov/pubmed/34493833 http://dx.doi.org/10.1038/s41390-021-01714-0 |
work_keys_str_mv | AT matchasaikumar pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia AT rajelstinanbu pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia AT mahadevanramya pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia AT rajuarunprasath pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia AT rajeshv pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia AT lewisleslieedward pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia AT mallayasamysurulivelrajan pharmacometricapproachtoassistdosageregimendesigninneonatesundergoingtherapeutichypothermia |