Prediction of maternal and fetal pharmacokinetics of indomethacin in pregnancy.
indomethacin
physiologically based pharmacokinetics
pregnant women
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
29
05
2021
received:
17
07
2020
accepted:
20
06
2021
pubmed:
30
6
2021
medline:
12
4
2022
entrez:
29
6
2021
Statut:
ppublish
Résumé
Indomethacin is used for the treatment of preterm labour, short cervices and idiopathic polyhydramnios during pregnancy. Few studies have described the pharmacokinetics (PK) of indomethacin during pregnancy. This study aimed to determine maternal and fetal PK of indomethacin during different trimesters of pregnancy using physiologically based PK (PBPK) modelling and simulations. Full PBPK simulations were performed in nonpregnant subjects and pregnant subjects from each trimester of pregnancy at steady state using Simcyp's healthy volunteers and pregnancy PBPK model, respectively. The fetal exposures were predicted using a fetoplacental pregnancy PBPK model. The models were verified by comparing PBPK-based predictions with observed PK profiles. Predicted exposure (AUC A mechanistic PBPK model adequately described the maternal and the fetal PK of indomethacin during pregnancy. As the pregnancy progresses, a modest decrease (≤32%) in systemic exposures in pregnant women and a 33% increase in fetal exposures to indomethacin were predicted. Higher fetal exposures in the third trimester of pregnancy may pose safety risks to the fetus. Additional studies are warranted to understand the exposure-response relationship and provide appropriate dosing recommendations during pregnancy that consider both safety and efficacy.
Substances chimiques
Indomethacin
XXE1CET956
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
271-281Subventions
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : U10HD047891
Informations de copyright
© 2021 British Pharmacological Society.
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