{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T23:15:36Z","timestamp":1767136536214,"version":"build-2238731810"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T00:00:00Z","timestamp":1547164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sophia Stichting Wetenschappelijk Onderzoek","award":["(S16-08)"],"award-info":[{"award-number":["(S16-08)"]}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Children undergoing cardiac surgery often receive acetaminophen (paracetamol) as part of their postoperative pain treatment. To date, there is no information on the pharmacokinetics (PK) of acetaminophen in this special population, even though differences, as a result of altered hemodynamics and\/or use of cardiopulmonary bypass, may be anticipated. Therefore, the aim of this study was to investigate the PK of intravenous acetaminophen in children after cardiac surgery with cardiopulmonary bypass. In the study, both children with and without Down syndrome were included. A population PK analysis, using NONMEM 7.2, was performed based on 161 concentrations of acetaminophen, acetaminophen sulfate, acetaminophen glucuronide, and oxidative metabolites from 17 children with Down syndrome and 13 children without Down syndrome of a previously published study (median age, 177 days [range, 92\u2013944], body weight, 6.1 kg [4.0\u201312.9]). All children received 3 intravenous acetaminophen doses of 7.5 mg\/kg (&lt;10 kg) or 15\u00a0mg\/kg (\u226510 kg) at 8\u2013hour intervals after cardiac surgery. For acetaminophen and its metabolites, 1\u2010compartment models were identified. Clearance of acetaminophen and metabolites increased linearly with body weight. Acetaminophen clearance in a typical child of 6.1 kg is 0.96 L\/h and volume of distribution 7.96 L. Down syndrome did not statistically significantly impact any of the PK parameters for acetaminophen, nor did any other remaining covariate. When comparing the PK parameters of acetaminophen in children after cardiac surgery with cardiopulmonary bypass with those from children of the same age following noncardiac surgery reported in the literature, clearance of acetaminophen was lower and volume of distribution higher.<\/jats:p>","DOI":"10.1002\/jcph.1373","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T08:54:45Z","timestamp":1547196885000},"page":"847-855","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Population Pharmacokinetic Modeling of Acetaminophen and Metabolites in Children After Cardiac Surgery With Cardiopulmonary Bypass"],"prefix":"10.1002","volume":"59","author":[{"given":"P.","family":"Mian","sequence":"first","affiliation":[{"name":"Intensive Care and Department of Paediatric Surgery Erasmus MC Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.J.","family":"Valkenburg","sequence":"additional","affiliation":[{"name":"Intensive Care and Department of Paediatric Surgery Erasmus MC Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Anesthesiology Erasmus MC  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Allegaert","sequence":"additional","affiliation":[{"name":"Intensive Care and Department of Paediatric Surgery Erasmus MC Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.C.P.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus MC  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.V.","family":"Breatnach","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care Medicine Our Lady's Children's Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.A.J.","family":"Knibbe","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University  Leiden The Netherlands"},{"name":"Department of Clinical Pharmacy St. Antonius Hospital  Nieuwegein The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Tibboel","sequence":"additional","affiliation":[{"name":"Intensive Care and Department of Paediatric Surgery Erasmus MC Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.H.J.","family":"Krekels","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.08.025"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2017-000046"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000379"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1980.tb01812.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1984.tb02495.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1986.tb02953.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1081\/CLT-120002882"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.104736"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198207020-00001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.5863\/1551-6776-16.4.246"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.259"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1461836"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/15748847113089990067"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/jcan.2002.29690"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3245"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1990.188"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000000904"},{"key":"e_1_2_10_19_1","unstructured":"PubChem. 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