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What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?

Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on...

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Autores principales: Šíma, Martin, Michaličková, Danica, Slanař, Ondřej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996486/
https://www.ncbi.nlm.nih.gov/pubmed/33668911
http://dx.doi.org/10.3390/pharmaceutics13030301
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author Šíma, Martin
Michaličková, Danica
Slanař, Ondřej
author_facet Šíma, Martin
Michaličková, Danica
Slanař, Ondřej
author_sort Šíma, Martin
collection PubMed
description Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15–20 mg/kg followed by a maintenance dose of 3–5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.
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spelling pubmed-79964862021-03-27 What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates? Šíma, Martin Michaličková, Danica Slanař, Ondřej Pharmaceutics Review Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15–20 mg/kg followed by a maintenance dose of 3–5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support. MDPI 2021-02-25 /pmc/articles/PMC7996486/ /pubmed/33668911 http://dx.doi.org/10.3390/pharmaceutics13030301 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
Šíma, Martin
Michaličková, Danica
Slanař, Ondřej
What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
title What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
title_full What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
title_fullStr What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
title_full_unstemmed What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
title_short What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
title_sort what is the best predictor of phenobarbital pharmacokinetics to use for initial dosing in neonates?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996486/
https://www.ncbi.nlm.nih.gov/pubmed/33668911
http://dx.doi.org/10.3390/pharmaceutics13030301
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