Rapid Increase in Clearance of Phenobarbital in Neonates on Extracorporeal Membrane Oxygenation: A Pilot Retrospective Population Pharmacokinetic Analysis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10415726" target="_blank" >RIV/00216208:11110/20:10415726 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/20:10415726

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Ii5eWyIERn" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Ii5eWyIERn</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/PCC.0000000000002402" target="_blank" >10.1097/PCC.0000000000002402</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Rapid Increase in Clearance of Phenobarbital in Neonates on Extracorporeal Membrane Oxygenation: A Pilot Retrospective Population Pharmacokinetic Analysis

Popis výsledku v původním jazyce

Objectives: This study characterizes the changes in the pharmacokinetics of phenobarbital associated with extracorporeal membrane oxygenation treatment in neonates, to illustrate our findings and provide guidance on dosing. Design: Retrospective pilot population pharmacokinetic analysis. Setting: Neonatal ICU. Patients: Thirteen critically ill neonates (birth body weight, 3.21kg [2.65-3.72 kg]; postnatal age at start of treatment: 2 d [0-7 d]; gestational age: 38wk [38-41 wk]) receiving venovenous or venoarterial extracorporeal membrane oxygenation. Interventions: Phenobarbital administered in a loading dose of 7.5mg/kg (8.5-16mg/kg) and maintenance dose of 6.9mg/kg/d (4.5-8.5mg/kg/d). Measurements and Main Results: Therapeutic drug monitoring data were available, yielding 5, 31, and 19 phenobarbital concentrations before, during, and after extracorporeal membrane oxygenation, respectively. Population pharmacokinetic analysis was performed using NONMEM 7.3.0 (ICON Development Solutions, Ellicott City, MD). Maturation functions for clearance and volume of distribution were obtained from literature. In a one-compartment model, clearance and volume of distribution for a typical neonate off extracorporeal membrane oxygenation and with a median birth body weight (3.21kg) at median postnatal age (2 d) were 0.0096L/hr (relative se = 11%)) and 2.72L (16%), respectively. During extracorporeal membrane oxygenation, clearance was found to linearly increase with time. Upon decannulation, phenobarbital clearance initially decreased and subsequently increased slowly driven by maturation. Extracorporeal membrane oxygenation-related changes in volume of distribution could not be identified, possibly due to sparse data collection shortly after extracorporeal membrane oxygenation start. According to the model, target attainment is achieved in the first 12 days of extracorporeal membrane oxygenation with a regimen of a loading dose of 20mg/kg and a maintenance dose of 4mg/kg/d divided in two doses with an increase of 0.25mg/kg every 12 hours during extracorporeal membrane oxygenation treatment. Conclusions: We found a time-dependent increase in phenobarbital clearance during the first 12 days of extracorporeal membrane oxygenation treatment in neonates, which results in continuously decreasing phenobarbital exposure and increases the risk of therapeutic failure over time. Due to high unexplained variability, frequent and repeated therapeutic drug monitoring should be considered even with the model-derived regimen.

Název v anglickém jazyce

Rapid Increase in Clearance of Phenobarbital in Neonates on Extracorporeal Membrane Oxygenation: A Pilot Retrospective Population Pharmacokinetic Analysis

Popis výsledku anglicky

Objectives: This study characterizes the changes in the pharmacokinetics of phenobarbital associated with extracorporeal membrane oxygenation treatment in neonates, to illustrate our findings and provide guidance on dosing. Design: Retrospective pilot population pharmacokinetic analysis. Setting: Neonatal ICU. Patients: Thirteen critically ill neonates (birth body weight, 3.21kg [2.65-3.72 kg]; postnatal age at start of treatment: 2 d [0-7 d]; gestational age: 38wk [38-41 wk]) receiving venovenous or venoarterial extracorporeal membrane oxygenation. Interventions: Phenobarbital administered in a loading dose of 7.5mg/kg (8.5-16mg/kg) and maintenance dose of 6.9mg/kg/d (4.5-8.5mg/kg/d). Measurements and Main Results: Therapeutic drug monitoring data were available, yielding 5, 31, and 19 phenobarbital concentrations before, during, and after extracorporeal membrane oxygenation, respectively. Population pharmacokinetic analysis was performed using NONMEM 7.3.0 (ICON Development Solutions, Ellicott City, MD). Maturation functions for clearance and volume of distribution were obtained from literature. In a one-compartment model, clearance and volume of distribution for a typical neonate off extracorporeal membrane oxygenation and with a median birth body weight (3.21kg) at median postnatal age (2 d) were 0.0096L/hr (relative se = 11%)) and 2.72L (16%), respectively. During extracorporeal membrane oxygenation, clearance was found to linearly increase with time. Upon decannulation, phenobarbital clearance initially decreased and subsequently increased slowly driven by maturation. Extracorporeal membrane oxygenation-related changes in volume of distribution could not be identified, possibly due to sparse data collection shortly after extracorporeal membrane oxygenation start. According to the model, target attainment is achieved in the first 12 days of extracorporeal membrane oxygenation with a regimen of a loading dose of 20mg/kg and a maintenance dose of 4mg/kg/d divided in two doses with an increase of 0.25mg/kg every 12 hours during extracorporeal membrane oxygenation treatment. Conclusions: We found a time-dependent increase in phenobarbital clearance during the first 12 days of extracorporeal membrane oxygenation treatment in neonates, which results in continuously decreasing phenobarbital exposure and increases the risk of therapeutic failure over time. Due to high unexplained variability, frequent and repeated therapeutic drug monitoring should be considered even with the model-derived regimen.

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

2020

Kód důvěrnosti údajů

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

Název periodika

Pediatric Critical Care Medicine

ISSN

1529-7535

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

"E707"-"E715"

Kód UT WoS článku

000571080600014

EID výsledku v databázi Scopus

2-s2.0-85090504984