{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:21:28Z","timestamp":1779164488341,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T00:00:00Z","timestamp":1587340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["836011022"],"award-info":[{"award-number":["836011022"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Racemic ibuprofen is widely used for the treatment of preterm neonates with patent ductus arteriosus. Currently used bodyweight\u2010based dosing guidelines are based on total ibuprofen, while only the S\u2010enantiomer of ibuprofen is pharmacologically active. We aimed to optimize ibuprofen dosing for preterm neonates of different ages based on an enantiomer\u2010specific population pharmacokinetic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We prospectively collected 210 plasma samples of 67 preterm neonates treated with ibuprofen for patent ductus arteriosus (median gestational age [GA] 26 [range 24\u201330] weeks, median body weight 0.83 [0.45\u20131.59] kg, median postnatal age [PNA] 3 [1\u201312] days), and developed a population pharmacokinetic model for S\u2010 and R\u2010ibuprofen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that S\u2010ibuprofen clearance (CL<jats:sub>S<\/jats:sub>, 3.98 mL\/h [relative standard error {RSE} 8%]) increases with PNA and GA, with exponents of 2.25 (RSE 6%) and 5.81 (RSE 15%), respectively. Additionally, a 3.11\u2010fold higher CL<jats:sub>S<\/jats:sub> was estimated for preterm neonates born small for GA (RSE 34%). Clearance of R\u2010ibuprofen was found to be high compared to CL<jats:sub>S<\/jats:sub> (18 mL\/h [RSE 24%]), resulting in a low contribution of R\u2010ibuprofen to total ibuprofen exposure. Current body weight was identified as covariate on both volume of distribution of S\u2010ibuprofen and R\u2010ibuprofen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>S\u2010ibuprofen clearance shows important maturation, especially with PNA, resulting in an up to 3\u2010fold increase in CL<jats:sub>S<\/jats:sub> during a 3\u2010day treatment regimen. This rapid increase in clearance needs to be incorporated in dosing guidelines by adjusting the dose for every day after birth to achieve equal ibuprofen exposure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14298","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T15:36:47Z","timestamp":1586187407000},"page":"2028-2039","source":"Crossref","is-referenced-by-count":20,"title":["Enantiomer specific pharmacokinetics of ibuprofen in preterm neonates with patent ductus arteriosus"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7230-0091","authenticated-orcid":false,"given":"Aline G.J.","family":"Engbers","sequence":"first","affiliation":[{"name":"Division of Systems Biomedicine &amp; Pharmacology, LACDR Leiden University  Leiden the Netherlands"},{"name":"Department of Paediatrics, Division of Neonatology Erasmus UMC \u2010 Sophia Children's Hospital  Rotterdam the 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Klerk","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Division of Neonatology Erasmus UMC \u2010 Sophia Children's Hospital  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irwin K.M.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Division of Neonatology Erasmus UMC \u2010 Sophia Children's Hospital  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Andriessen","sequence":"additional","affiliation":[{"name":"Department of Neonatology M\u00e1xima Medical Centre  Veldhoven the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kian D.","family":"Liem","sequence":"additional","affiliation":[{"name":"Department of Neonatology Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter 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