Monfort, Anaëlle; Cardoso, Evelina; Eap, Chin B; Ansermot, Nicolas; Crettol, Severine; Fischer Fumeaux, Céline J; Graz, Myriam Bickle; Harari, Mathilde Morisod; Weisskopf, Etienne; Gandia, Peggy; Allegaert, Karel; Annaert, Pieter; Nordeng, Hedvig; Hascoët, Jean-Michel; Claris, Olivier; Epiney, Manuella; Ferreira, Ema; Leclair, Grégoire; Csajka, Chantal; Panchaud, Alice; ... (2024). A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project. (In Press). British journal of clinical pharmacology Wiley 10.1111/bcp.16177
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Brit_J_Clinical_Pharma_-_2024_-_Monfort_-_A_population_pharmacokinetic_model_for_sertraline_in_women_during_the_perinatal.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (1MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM) |
UniBE Contributor: |
Panchaud Monnat, Alice Elke Martine |
Subjects: |
600 Technology > 610 Medicine & health 300 Social sciences, sociology & anthropology > 360 Social problems & social services |
ISSN: |
1365-2125 |
Publisher: |
Wiley |
Funders: |
[222] Horizon 2020 ; [4] Swiss National Science Foundation |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
22 Jul 2024 16:10 |
Last Modified: |
24 Jul 2024 08:39 |
Publisher DOI: |
10.1111/bcp.16177 |
PubMed ID: |
39030897 |
Additional Information: |
Alice Panchaud and Monia Guidi contributed equally to this work. |
Uncontrolled Keywords: |
breastfeeding infant exposure population pharmacokinetic modelling pregnancy sertraline |
BORIS DOI: |
10.48350/199118 |
URI: |
https://boris.unibe.ch/id/eprint/199118 |
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