{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:21:30Z","timestamp":1779164490325,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Spontaneous closure of the ductus arteriosus depends on gestational age (GA) and might be delayed in preterm infants, resulting in patent ductus arteriosus (PDA). Ibuprofen can be administered to enhance closure, but the exposure\u2010response relationship between ibuprofen and the closure of PDA remains uncertain. We investigated the influence of patient characteristics and ibuprofen exposure on ductus closure. A cohort of preterm infants with PDA and treated with ibuprofen was analyzed. Ibuprofen exposure was based on a previously developed population pharmacokinetic study that was in part based on the same study population. Logistic regression analyses were performed with ductus closure (yes\/no) as outcome, to analyze the contribution of ibuprofen exposure and patient characteristics. In our cohort of 263 preterm infants (median GA 26.1 (range: 23.7\u201330.0) weeks, birthweight 840 (365\u20131,470) g) receiving ibuprofen treatment consisting of 3 doses that was initiated at a median postnatal age (PNA<jats:sub>start<\/jats:sub>) of 5 (1\u201332) days, PDA was closed in 55 (21%) patients. Exposure to ibuprofen strongly decreased with PNA<jats:sub>start<\/jats:sub>. Overall, the probability of ductus closure decreased with PNA<jats:sub>start<\/jats:sub> (odds ratio (OR): 0.7, 95% CI: 0.6\u20130.8) and <jats:italic>Z<\/jats:italic>\u2010score for birthweight (<jats:italic>Z<\/jats:italic><jats:sub>Birthweight\u2010for\u2010GA<\/jats:sub>; OR: 0.8, 95% CI: 0.6\u20101.0), and increased with GA (OR: 1.5, 95% CI: 1.1\u20131.9). For patients with PNA<jats:sub>start<\/jats:sub>\u00a0&lt;\u00a01\u00a0week, concentrations of ibuprofen, GA, and <jats:italic>Z<\/jats:italic><jats:sub>Birthweight\u2010for\u2010GA<\/jats:sub> predicted probability of ductus closure. During a window of opportunity for ductus closure within the first days of life, probability of closure depends on GA, <jats:italic>Z<\/jats:italic><jats:sub>Birthweight\u2010for\u2010GA<\/jats:sub>, and ibuprofen exposure. Increased, yet unstudied dosages might increase the effectivity of ibuprofen beyond the first week of life.<\/jats:p>","DOI":"10.1002\/cpt.2616","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T16:35:56Z","timestamp":1650126956000},"page":"307-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Effect of Ibuprofen Exposure and Patient Characteristics on the Closure of the Patent Ductus Arteriosus in Preterm Infants"],"prefix":"10.1111","volume":"112","author":[{"given":"Aline G. J.","family":"Engbers","sequence":"first","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology LACDR Leiden University  Leiden The Netherlands"},{"name":"Division of Neonatology Department of Paediatrics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swantje","family":"V\u00f6ller","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology LACDR Leiden University  Leiden The Netherlands"},{"name":"Pharmacy LACDR Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Flint","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Paediatrics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"},{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiaan C.","family":"Goulooze","sequence":"additional","affiliation":[{"name":"Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&amp;P)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"de Klerk","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Paediatrics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke H. J.","family":"Krekels","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology LACDR Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sten P.","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Biostatistics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irwin K. M.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Paediatrics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherijne A. J.","family":"Knibbe","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology LACDR Leiden University  Leiden The Netherlands"},{"name":"Division of Neonatology Department of Paediatrics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"},{"name":"Department of Clinical Pharmacy St Antonius Hospital  Nieuwegein The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinno H. P.","family":"Simons","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Paediatrics Erasmus UMC \u2010 Sophia Children\u2019s Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3506"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0387-7"},{"key":"e_1_2_10_4_1","first-page":"52","article-title":"Pharmacotherapy for patent ductus arteriosus closure","volume":"14","author":"Ferguson J.M.","year":"2018","journal-title":"Congenit. 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