Severity parameters for asphyxia or hypoxic-ischemic encephalopathy do not explain inter-individual variability in the pharmacokinetics of phenobarbital in newborns treated with therapeutic hypothermia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10444940" target="_blank" >RIV/00064165:_____/22:10444940 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10444940

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=grepJEbewk" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=grepJEbewk</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.23736/S2724-5276.20.05740-0" target="_blank" >10.23736/S2724-5276.20.05740-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Severity parameters for asphyxia or hypoxic-ischemic encephalopathy do not explain inter-individual variability in the pharmacokinetics of phenobarbital in newborns treated with therapeutic hypothermia

Popis výsledku v původním jazyce

BACKGROUND: The current study uses a population modeling approach to evaluate and quantify the impact of severity of asphyxia and hypoxic-ischemic encephalopathy (HIE) on the pharmacokinetics of phenobarbital in asphyxiated newborns treated with therapeutic hypothermia. METHODS: Included newborns received phenobarbital (the TOBY trial protocol). 120 plasma samples were available from 50 newborns, median (IQR) weight 3.3 (2.8-3.5) kg and gestational age 39 (39-40) weeks. NONMEM(R) version 7.2 was used for the data analysis. Age, body weight, sex, concomitant medications, kidney and liver function markers, as well as severity parameters of asphyxia and HIE were tested as potential covariates of pharmacokinetics of phenobarbital. Severe asphyxia was defined as pH of arterial umbilical cord blood &lt;=7.1 and Apgar 5 &lt;=5, and severe HIE was defined as time to normalization of amplitude-integrated electroencephalography (aEEG) &gt;24 h. RESULTS: Weight was found to be the only statistically significant covariate for the volume of distribution. At weight of 1 kg volume of distribution was 0.91 L and for every additional kg it increased in 0.91 L. Clearance was 0.00563 L/h. No covariates were statistically significant for the clearance of phenobarbital. CONCLUSIONS: Phenobarbital dose adjustments are not indicated in the studied population, irrespective of the severity of asphyxia or HIE.

Název v anglickém jazyce

Severity parameters for asphyxia or hypoxic-ischemic encephalopathy do not explain inter-individual variability in the pharmacokinetics of phenobarbital in newborns treated with therapeutic hypothermia

Popis výsledku anglicky

BACKGROUND: The current study uses a population modeling approach to evaluate and quantify the impact of severity of asphyxia and hypoxic-ischemic encephalopathy (HIE) on the pharmacokinetics of phenobarbital in asphyxiated newborns treated with therapeutic hypothermia. METHODS: Included newborns received phenobarbital (the TOBY trial protocol). 120 plasma samples were available from 50 newborns, median (IQR) weight 3.3 (2.8-3.5) kg and gestational age 39 (39-40) weeks. NONMEM(R) version 7.2 was used for the data analysis. Age, body weight, sex, concomitant medications, kidney and liver function markers, as well as severity parameters of asphyxia and HIE were tested as potential covariates of pharmacokinetics of phenobarbital. Severe asphyxia was defined as pH of arterial umbilical cord blood &lt;=7.1 and Apgar 5 &lt;=5, and severe HIE was defined as time to normalization of amplitude-integrated electroencephalography (aEEG) &gt;24 h. RESULTS: Weight was found to be the only statistically significant covariate for the volume of distribution. At weight of 1 kg volume of distribution was 0.91 L and for every additional kg it increased in 0.91 L. Clearance was 0.00563 L/h. No covariates were statistically significant for the clearance of phenobarbital. CONCLUSIONS: Phenobarbital dose adjustments are not indicated in the studied population, irrespective of the severity of asphyxia or HIE.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Minerva Pediatrics

ISSN

2724-5276

e-ISSN

2724-5780

Svazek periodika

74

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

IT - Italská republika

Počet stran výsledku

9

Strana od-do

107-115

Kód UT WoS článku

000795673900002

EID výsledku v databázi Scopus

2-s2.0-85129997611