{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:01:58Z","timestamp":1780286518021,"version":"3.54.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV\u2010023795"],"award-info":[{"award-number":["INV\u2010023795"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To establish an optimized sotalol dosing strategy for fetal tachycardia using a pregnancy physiologically based pharmacokinetic (PBPK) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      A verified PBPK model was developed incorporating pregnancy\u2010induced physiological changes and placental transfer. Simulations were performed to evaluate current dosing recommendations and alternative dosing scenarios were explored. To avoid maternal dose\u2010related toxicity (QT\u2010prolongation), we aimed for maternal concentrations &lt; 2.5\u00a0mg\/L. Based on neonatal concentration\u2010effect data, we aimed for fetal C\n                      <jats:sub>trough<\/jats:sub>\n                      concentrations of 0.4\u20131.0\u00a0mg\/L.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Model predictions for maternal and fetal plasma concentrations were generally consistent with available maternal and fetal exposure data. Simulations showed that at the maximum oral daily dose of 480\u00a0mg, 16% of maternal concentrations exceeded the toxicity threshold, while 90% of fetuses had therapeutic C\n                      <jats:sub>trough<\/jats:sub>\n                      levels. Reducing the daily dose to 400\u00a0mg lowered maternal overexposure to 0.1%, with 87% of fetuses still reaching therapeutic levels. Additionally, splitting the 480\u00a0mg dose into three administrations per day reduced maternal overexposure to 0.3% and increased fetal target attainment to 95%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pregnancy PBPK modeling is a valuable tool for optimizing fetal sotalol therapy. A daily dose not exceeding 400\u00a0mg, or dividing daily doses of 240\u00a0mg and higher into three administrations, may optimize the balance between predicted fetal efficacy and maternal toxicity risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.70104","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:20:40Z","timestamp":1772961640000},"page":"533-540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sotalol Dose Optimization for Fetal Tachycardia: A Pregnancy Physiologically Based Pharmacokinetic Model Study"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-2862","authenticated-orcid":false,"given":"Hedwig","family":"van Hove","sequence":"first","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce E. M.","family":"van der Heijden","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"van Uden","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violette M. G. J.","family":"Gijsen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Greupink","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia N.","family":"de Wildt","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Department of Neonatal and Pediatric Intensive Care Erasmus MC\u2010Sophia Children's Hospital  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"van Drongelen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052\u2010020\u20100785\u20109"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ipej.2019.02.007"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.12390"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.01.388"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.101.23.2721"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.13111"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753495x18808118"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.06.024"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00065"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00609896"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109149(93)90021\u20104"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.687978"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010013\u20109555\u20106"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2020.28.e14"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1491"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2012.02.005"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12479"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735\u20101097(03)00779\u20104"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102017\u2010016597"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2008.03.026"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.026120"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/11597440\u2010000000000\u201000000"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109149(86)90692\u20102"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1982.122"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.06.061"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/mjt.0b013e3181ea3184"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00278585"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010020\u201000861\u20107"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1979.tb04737.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24031848"},{"key":"e_1_2_11_32_1","volume-title":"Seminars in Fetal and Neonatal Medicine","author":"Jaeggi E. 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