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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

The result's identifiers

  • Result code in 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>

  • Alternative codes found

    RIV/00216208:11110/22:10444940

  • Result on the web

    <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>

Alternative languages

  • Result language

    angličtina

  • Original language name

    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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30104 - Pharmacology and pharmacy

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2022

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Minerva Pediatrics

  • ISSN

    2724-5276

  • e-ISSN

    2724-5780

  • Volume of the periodical

    74

  • Issue of the periodical within the volume

    2

  • Country of publishing house

    IT - ITALY

  • Number of pages

    9

  • Pages from-to

    107-115

  • UT code for WoS article

    000795673900002

  • EID of the result in the Scopus database

    2-s2.0-85129997611