{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:34:26Z","timestamp":1792010066518,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201908500113"],"award-info":[{"award-number":["201908500113"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To enhance understanding of betamethasone and its metabolites' pharmacokinetics in pregnancy, specifically early\u2010onset pre\u2010eclampsia, through a population pharmacokinetic model. Additionally, to investigate the placental metabolism and transfer of betamethasone and its main metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective, single\u2010centre pharmacokinetic study was conducted in pregnant women (<jats:italic>n\u2009=<\/jats:italic>\u00a028) with imminent preterm birth treated with intramuscular betamethasone. Betamethasone serum concentrations were determined from serial venous blood samples (<jats:italic>n\u2009=<\/jats:italic>\u00a0194). Placental transfer and metabolism were studied using ex vivo human placental perfusion (healthy term; <jats:italic>n\u2009=<\/jats:italic>\u00a03) and placental explant experiments (healthy term, <jats:italic>n\u2009=<\/jats:italic>\u00a04; early\u2010onset pre\u2010eclampsia, <jats:italic>n\u2009=<\/jats:italic>\u00a04). Additionally, placental mRNA expression of CYP3A4, CYP3A7, 11\u03b2\u2010hydroxysteroid dehydrogenase (HSD) 1 and 11\u03b2\u2010HSD2 were quantified in healthy and early\u2010onset pre\u2010eclampsia placentas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The population pharmacokinetic model was best described by a 2\u2010compartment nonlinear mixed effects model. Betamethasone clearance in early\u2010onset pre\u2010eclamptic women was 60% lower of that observed in women without pre\u2010eclampsia (9.35 <jats:italic>vs<\/jats:italic>. 15.78\u2009L\/h), resulting in a 40% median increase in maternal betamethasone exposure (1567 <jats:italic>vs<\/jats:italic>. 1114\u2009ng\u00a0h\/mL). Ex vivo experiments showed placental transfer of betamethasone to the foetal circulation (foetal\u2010to\u2010maternal ratio 0.76\u2009\u00b1\u00a00.05 [in a perfused placental cotyledon]). The placenta only converted betamethasone into 11\u2010ketobetamethasone, with similar ratios in early\u2010onset pre\u2010eclampsia and healthy placental explants (3.0\u00a0\u00b1\u00a02.2 <jats:italic>vs<\/jats:italic>. 1.4\u00a0\u00b1\u00a00.4 per mg tissue, <jats:italic>P =<\/jats:italic> .27). The expression of 11\u03b2\u2010HSD1 mRNA was lower in early\u2010onset pre\u2010eclampsia placentas (<jats:italic>P =<\/jats:italic> .015), while placental CYP3A7 and 11\u03b2\u2010HSD2 mRNA expression were similar.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Women with early\u2010onset pre\u2010eclampsia have elevated betamethasone exposure. Betamethasone transfers freely into the foetal circulation, with placental metabolism resulting only in 11\u2010ketobetamethasone. Decreased placental 11\u03b2\u2010HSD1 expression may play a role in increased betamethasone exposure in early\u2010onset pre\u2010eclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70035","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T02:38:56Z","timestamp":1741919936000},"page":"2327-2339","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics of betamethasone in pre\u2010eclampsia: An in vivo and ex vivo study"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-6159","authenticated-orcid":false,"given":"Sam","family":"Schoenmakers","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4692-9689","authenticated-orcid":false,"given":"Letao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-372X","authenticated-orcid":false,"given":"Anna C. M.","family":"Kluivers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"},{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4736-398X","authenticated-orcid":false,"given":"Michelle","family":"Broekhuizen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Neonatology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-1103","authenticated-orcid":false,"given":"Madhavi S.","family":"Harhangi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine Erasmus MC University Medical Center Rotterdam  Rotterdam the Netherlands"},{"name":"Department of Internal Medicine, Division of Pharmacology and Vascular Medicine Erasmus MC University Hospital  Rotterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Neonatology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-3585","authenticated-orcid":false,"given":"A. 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