Pharmacokinetics of Midazolam in preterm neonates with an insight in brain Tissue: A PBPK approach.
Pak J Pharm Sci
; 35(5): 1459-1465, 2022 Sep.
Article
em En
| MEDLINE
| ID: mdl-36451576
ABSTRACT
Physiological maturity is a gradual process taking place throughout infancy and childhood. Though for years anatomical growth has been the basis for dose calculation in pediatric population, physiological immaturity can-not be overlooked especially in neonates. The potential difference in physiology can significantly affect the outcomes of treatment and may result in under dosing or over-dosage. For many ethical and logistic constrains, carrying out pharmacokinetic studies of pharmacological agents in neonatal population remains a challenging task and such data is therefore, insufficient. This work presents Physiologically Based Pharmacokinetic modeling approach to predict the disposition of IV Midazolam in preterm neonates of different gestational ages, validated by the experimental studies. Furthermore, midazolam concentration in brain tissue of these neonates- the major site of its action- has been noted. The predicted and observed plasma pharmacokinetic parameters are comparable. This article demonstrates the usefulness of in-silico approach for finding out the PK parameters in neonates which may aid in deciding the frequency of drug administration in this population.
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Base de dados:
MEDLINE
Assunto principal:
Midazolam
/
Encéfalo
Tipo de estudo:
Prognostic_studies
Limite:
Child
/
Humans
/
Newborn
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article