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Model-based clinical dose optimization for phenobarbital in neonates: An illustration of the importance of data sharing and external validation

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10365439" target="_blank" >RIV/00216208:11110/17:10365439 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00064165:_____/17:10365439

  • Výsledek na webu

    <a href="http://dx.doi.org/10.1016/j.ejps.2017.05.026" target="_blank" >http://dx.doi.org/10.1016/j.ejps.2017.05.026</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.ejps.2017.05.026" target="_blank" >10.1016/j.ejps.2017.05.026</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Model-based clinical dose optimization for phenobarbital in neonates: An illustration of the importance of data sharing and external validation

  • Popis výsledku v původním jazyce

    Background: Particularly in the pediatric clinical pharmacology field, data-sharing offers the possibility of making the most of all available data. In this study, we utilize previously collected therapeutic drug monitoring (TDM) data of term and preterm newborns to develop a population pharmacokinetic model for phenobarbital. We externally validate the model using prospective phenobarbital data from an ongoing pharmacokinetic study in preterm neonates. Methods: TDM data from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2.7 (0.45-4.5) kg; postnatal age (PNA): 4.5 (0 - 22) days) contained information on dosage histories, concentration and covariate data (including birth weight, actual weight, post-natal age (PNA), postmenstrual age, GA, sex, liver and kidney function, APGAR-score). Model development was carried out using NONMEM (R) 7.3. After assessment of model fit, the model was validated using data of 17 neonates included in the DINO (Drug dosage Improvement in NeOnates)-study. Results: Modelling of 229 plasma concentrations, ranging from 3.2 to 75.2 mg/L, resulted in a one compartment model for phenobarbital. Clearance (CL) and volume (V-d) for a child with a birthweight of 2.6 kg at PNA day 4.5 was 0.0091 L/h (9%) and 2.38 L (5%), respectively. Birthweight and PNA were the best predictors for CL maturation, increasing CL by 36.7% per kg birthweight and 5.3% per postnatal day of living, respectively. The best predictor for the increase in Vd was actual bodyweight (0.31 L/kg). External validation showed that the model can adequately predict the pharmacokinetics in a prospective study. Conclusion: Data-sharing can help to successfully develop and validate population pharmacokinetic models in neonates. From the results it seems that both PNA and bodyweight are required to guide dosing of phenobarbital in term and preterm neonates.

  • Název v anglickém jazyce

    Model-based clinical dose optimization for phenobarbital in neonates: An illustration of the importance of data sharing and external validation

  • Popis výsledku anglicky

    Background: Particularly in the pediatric clinical pharmacology field, data-sharing offers the possibility of making the most of all available data. In this study, we utilize previously collected therapeutic drug monitoring (TDM) data of term and preterm newborns to develop a population pharmacokinetic model for phenobarbital. We externally validate the model using prospective phenobarbital data from an ongoing pharmacokinetic study in preterm neonates. Methods: TDM data from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2.7 (0.45-4.5) kg; postnatal age (PNA): 4.5 (0 - 22) days) contained information on dosage histories, concentration and covariate data (including birth weight, actual weight, post-natal age (PNA), postmenstrual age, GA, sex, liver and kidney function, APGAR-score). Model development was carried out using NONMEM (R) 7.3. After assessment of model fit, the model was validated using data of 17 neonates included in the DINO (Drug dosage Improvement in NeOnates)-study. Results: Modelling of 229 plasma concentrations, ranging from 3.2 to 75.2 mg/L, resulted in a one compartment model for phenobarbital. Clearance (CL) and volume (V-d) for a child with a birthweight of 2.6 kg at PNA day 4.5 was 0.0091 L/h (9%) and 2.38 L (5%), respectively. Birthweight and PNA were the best predictors for CL maturation, increasing CL by 36.7% per kg birthweight and 5.3% per postnatal day of living, respectively. The best predictor for the increase in Vd was actual bodyweight (0.31 L/kg). External validation showed that the model can adequately predict the pharmacokinetics in a prospective study. Conclusion: Data-sharing can help to successfully develop and validate population pharmacokinetic models in neonates. From the results it seems that both PNA and bodyweight are required to guide dosing of phenobarbital in term and preterm neonates.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30209 - Paediatrics

Návaznosti výsledku

  • Projekt

  • Návaznosti

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Ostatní

  • Rok uplatnění

    2017

  • Kód důvěrnosti údajů

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

Údaje specifické pro druh výsledku

  • Název periodika

    European Journal of Pharmaceutical Sciences

  • ISSN

    0928-0987

  • e-ISSN

  • Svazek periodika

    109

  • Číslo periodika v rámci svazku

    Supplement

  • Stát vydavatele periodika

    NL - Nizozemsko

  • Počet stran výsledku

    8

  • Strana od-do

    "S90"-"S97"

  • Kód UT WoS článku

    000415283100016

  • EID výsledku v databázi Scopus

    2-s2.0-85019364127