TY - JOUR
T1 - A population pharmacokinetic model for sertraline in women during the perinatal period—A contribution from the ConcePTION project
AU - Monfort, Anaëlle
AU - Cardoso, Evelina
AU - Eap, Chin B.
AU - collaborators of the SSRI Breast Milk study
AU - Ansermot, Nicolas
AU - Crettol, Severine
AU - Fischer Fumeaux, Céline J.
AU - Graz, Myriam Bickle
AU - Harari, Mathilde Morisod
AU - Weisskopf, Etienne
AU - Gandia, Peggy
AU - Allegaert, Karel
AU - Annaert, Pieter
AU - Nordeng, Hedvig
AU - Hascoët, Jean Michel
AU - Claris, Olivier
AU - Epiney, Manuella
AU - Ferreira, Ema
AU - Leclair, Grégoire
AU - Csajka, Chantal
AU - Panchaud, Alice
AU - Guidi, Monia
N1 - Publisher Copyright:
© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2024/11
Y1 - 2024/11
N2 - Aims: 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. Methods: 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. Results: 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−1 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−1 after maternal daily doses between 25 and 150 mg. Conclusions: 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.
AB - Aims: 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. Methods: 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. Results: 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−1 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−1 after maternal daily doses between 25 and 150 mg. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85198938634&partnerID=8YFLogxK
U2 - 10.1111/bcp.16177
DO - 10.1111/bcp.16177
M3 - Article
C2 - 39030897
AN - SCOPUS:85198938634
SN - 0306-5251
VL - 90
SP - 2849
EP - 2860
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 11
ER -