A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project

Anaëlle Monfort^{1

2}, Evelina Cardoso³, Chin B Eap^{4

5

6

7}, Nicolas Ansermot⁷, Severine Crettol⁷, Céline J Fischer Fumeaux⁸, Myriam Bickle Graz⁸, Mathilde Morisod Harari⁹, Etienne Weisskopf⁴, Peggy Gandia¹⁰, Karel Allegaert^{11

12

13}, Pieter Annaert¹⁴, Hedvig Nordeng¹⁵, Jean-Michel Hascoët¹⁶, Olivier Claris^{17

18}, Manuella Epiney¹⁹, Ema Ferreira^{1

2}, Grégoire Leclair², Chantal Csajka^{4

5

6}, Alice Panchaud^{3

20}, Monia Guidi^{4

6

21}; collaborators of the SSRI Breast Milk study

Affiliations

¹ CHU Sainte-Justine, Montréal, QC, Canada.
² Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada.
³ Service of Pharmacy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵ School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
⁶ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva and University of Lausanne, Lausanne and Geneva, Switzerland.
⁷ Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
⁸ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital, Lausanne, Switzerland.
⁹ Division of Child and Adolescent Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
¹⁰ Laboratory of Pharmacokinetics and Toxicology, Purpan Hospital, University Hospital of Toulouse, Toulouse, France.
¹¹ Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
¹² Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
¹³ Department of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands.
¹⁴ Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
¹⁵ Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, Oslo, Norway.
¹⁶ Department of Neonatology, Maternité Régionale, Université de Lorraine, Nancy, France.
¹⁷ Department of Neonatology, Hospices Civils de Lyon, Lyon, France.
¹⁸ Claude Bernard University, Lyon, France.
¹⁹ Department of Women, Child and Adolescent, Geneva University Hospital, Geneva, Switzerland.
²⁰ Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
²¹ Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

PMID: 39030897
DOI: 10.1111/bcp.16177

Free article

Multicenter Study

A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project

Anaëlle Monfort et al. Br J Clin Pharmacol. 2024 Nov.

Free article

. 2024 Nov;90(11):2849-2860.

doi: 10.1111/bcp.16177. Epub 2024 Jul 19.

Authors

Affiliations

¹ CHU Sainte-Justine, Montréal, QC, Canada.
² Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada.
³ Service of Pharmacy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁴ Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵ School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
⁶ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva and University of Lausanne, Lausanne and Geneva, Switzerland.
⁷ Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
⁸ Clinic of Neonatology, Department Mother-Woman-Child, Lausanne University Hospital, Lausanne, Switzerland.
⁹ Division of Child and Adolescent Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
¹⁰ Laboratory of Pharmacokinetics and Toxicology, Purpan Hospital, University Hospital of Toulouse, Toulouse, France.
¹¹ Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
¹² Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
¹³ Department of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands.
¹⁴ Drug Delivery and Disposition Lab, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
¹⁵ Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, Oslo, Norway.
¹⁶ Department of Neonatology, Maternité Régionale, Université de Lorraine, Nancy, France.
¹⁷ Department of Neonatology, Hospices Civils de Lyon, Lyon, France.
¹⁸ Claude Bernard University, Lyon, France.
¹⁹ Department of Women, Child and Adolescent, Geneva University Hospital, Geneva, Switzerland.
²⁰ Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
²¹ Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

PMID: 39030897
DOI: 10.1111/bcp.16177

Abstract

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.

Keywords: breastfeeding; infant exposure; population pharmacokinetic modelling; pregnancy; sertraline.

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References

REFERENCES

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A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project

Affiliations

A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical