A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project.
Détails
ID Serval
serval:BIB_09F8B14E5C96
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project.
Périodique
British journal of clinical pharmacology
Collaborateur⸱rice⸱s
collaborators of the SSRI Breast Milk study
ISSN
1365-2125 (Electronic)
ISSN-L
0306-5251
Statut éditorial
In Press
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Publication Status: aheadofprint
Résumé
Sertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability.
Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted.
Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 μg kg <sup>-1</sup> after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL <sup>-1</sup> after maternal daily doses between 25 and 150 mg.
Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding.
Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted.
Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 μg kg <sup>-1</sup> after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL <sup>-1</sup> after maternal daily doses between 25 and 150 mg.
Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding.
Mots-clé
breastfeeding, infant exposure, population pharmacokinetic modelling, pregnancy, sertraline
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/07/2024 14:20
Dernière modification de la notice
20/08/2024 7:23