{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:34:24Z","timestamp":1792010064022,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Despite antenatal corticosteroids therapy, respiratory distress syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date, the relationship between <jats:italic>in utero<\/jats:italic> fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS. Pregnant women &gt;\u00a027\u00a0weeks\u2019 gestation and who received at least a single dose of betamethasone for prevention of RDS were enrolled. Maternal, cord blood, and amniotic fluid betamethasone time\u2010courses were analyzed using the Monolix software. A total of 220 maternal blood, 56 cord blood, and 26 amniotic fluid samples were described by a two\u2010compartment model with two effect compartments linked by rate transfer constants. Apparent clearances and volumes of distribution parameters were allometrically scaled for a 70\u00a0kg third trimester pregnant woman. The impact of a twin pregnancy was found to increase maternal clearance by 28%. Using a fetal\u2010to\u2010mother exposure ratio, the median (95% confidence interval (CI)) transplacental transfer of betamethasone was estimated to 35% (95% CI 0.11\u20130.67). After adjustment for gestational age and twin pregnancy, RDS was found to be associated to the time spent <jats:italic>in utero<\/jats:italic> below quantifiable concentrations (i.e., &lt;\u00a01\u00a0ng\/mL): odds ratio of 1.10 (95% CI 1.01\u20131.19) per day increase (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Trying to take into account both efficacy and safety, we simulated different dosing schemes in order to maintain a maximum of fetuses above 1\u00a0ng\/mL without exceeding the total standard dose.<\/jats:p>","DOI":"10.1002\/cpt.1887","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T03:04:04Z","timestamp":1589252644000},"page":"1026-1035","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Maternal Betamethasone for Prevention of Respiratory Distress Syndrome in Neonates: Population Pharmacokinetic and Pharmacodynamic Approach"],"prefix":"10.1111","volume":"108","author":[{"given":"Frantz","family":"Foissac","sequence":"first","affiliation":[{"name":"Pediatric and Perinatal Drug Evaluation and Pharmacology Universit\u00e9 de Paris Paris France"},{"name":"URC\/CIC Paris Descartes Necker Cochin Necker\u2010Enfants Malades Hospital Assistance Publique \u2013 H\u00f4pitaux de Paris (AP\u2010HP) Paris France"},{"name":"CIC\u20101419 Inserm, Cochin\u2010Necker Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Pediatric and Perinatal Drug Evaluation and Pharmacology Universit\u00e9 de Paris Paris France"},{"name":"Clinical Pharmacology Department AP\u2010HP Paris Centre Hospital Group Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9borah","family":"Hirt","sequence":"additional","affiliation":[{"name":"Pediatric and Perinatal Drug Evaluation and Pharmacology Universit\u00e9 de Paris Paris France"},{"name":"Clinical Pharmacology Department AP\u2010HP Paris Centre Hospital Group Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Lui","sequence":"additional","affiliation":[{"name":"Pediatric and Perinatal Drug Evaluation and Pharmacology Universit\u00e9 de Paris Paris France"},{"name":"Clinical Pharmacology Department AP\u2010HP Paris Centre Hospital Group Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efm","family":"Bouazza","sequence":"additional","affiliation":[{"name":"Pediatric and Perinatal Drug Evaluation and Pharmacology Universit\u00e9 de Paris Paris France"},{"name":"URC\/CIC Paris Descartes Necker Cochin Necker\u2010Enfants Malades Hospital Assistance Publique \u2013 H\u00f4pitaux de Paris (AP\u2010HP) Paris France"},{"name":"CIC\u20101419 Inserm, Cochin\u2010Necker Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Ville","sequence":"additional","affiliation":[{"name":"Maternity H\u00f4pital Necker \u2013 Enfants Malades AP\u2010HP Paris France"},{"name":"EA 7328 Paris Descartes University Sorbonne Paris Cit\u00e9 Paris 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