{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:57:47Z","timestamp":1790063867990,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_135650"],"award-info":[{"award-number":["320030_135650"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI\u2010Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk\u2010to\u2010plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model\u2010based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010eight 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\u00a0\u03bcg\u2009kg<jats:sup>\u22121<\/jats:sup> after a 50\u2009mg maternal daily dose, representing 0.95% of the weight\u2010adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23\u2009ng\u2009mL<jats:sup>\u22121<\/jats:sup> after maternal daily doses between 25 and 150\u2009mg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16177","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T08:20:15Z","timestamp":1721377215000},"page":"2849-2860","source":"Crossref","is-referenced-by-count":10,"title":["A population pharmacokinetic model for sertraline in women during the perinatal period\u2014A contribution from the ConcePTION 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