A Population Pharmacokinetic Model of Pentobarbital for Children with Status Epilepticus and Severe Traumatic Brain Injury.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
accepted:
30
03
2023
medline:
14
7
2023
pubmed:
29
5
2023
entrez:
29
5
2023
Statut:
ppublish
Résumé
Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI). To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations. Develop a PopPK model with non-linear mixed-effects modelling (NONMEM A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (V The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children.
Sections du résumé
BACKGROUND
Pentobarbital pharmacokinetics (PK) remain elusive and the therapeutic windows narrow. Administration is frequent in critically ill children with refractory status epilepticus (SE) and severe traumatic brain injury (sTBI).
OBJECTIVES
To investigate pentobarbital PK in SE and sTBI patients admitted to the paediatric intensive care unit (PICU) with population-based PK (PopPK) modelling and dosing simulations.
METHODS
Develop a PopPK model with non-linear mixed-effects modelling (NONMEM
RESULTS
A one-compartment PK model with allometrically scaled weight on clearance (CL; 0.75) and volume of distribution (V
CONCLUSIONS
The one-compartment PK model of intravenous pentobarbital described data well whereby serum creatinine and CRP significantly correlated with pentobarbital CL. Dosing simulations formulated adjusted dosing advice in patients with elevated creatinine and/or CRP. Prospective PK studies with pharmacodynamic endpoints, are imperative to optimise pentobarbital dosing in terms of safety and clinical efficacy in critically ill children.
Identifiants
pubmed: 37247187
doi: 10.1007/s40262-023-01249-z
pii: 10.1007/s40262-023-01249-z
pmc: PMC10338388
doi:
Substances chimiques
Anti-Bacterial Agents
0
Pentobarbital
I4744080IR
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1011-1022Informations de copyright
© 2023. The Author(s).
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