{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:09:35Z","timestamp":1788858575055,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005111","name":"Rigshospitalet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007403","name":"Dagmar Marshalls Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007403","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008267","name":"Kong Christian den Tiendes Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008267","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Melatonin may have several beneficial clinical effects in the perioperative setting. In children, it has been studied for preoperative anxiety, postoperative pain, and emergence delirium. Melatonin's pharmacokinetic profile is well\u2010known in adults, but data in young children are sparse. We aimed to investigate the pharmacokinetic parameters of an intravenous intraoperative bolus of melatonin in pediatric surgical patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We enrolled 20 participants aged 1\u20136\u2009years undergoing general anesthesia for elective surgery to receive an intravenous melatonin dose of 0.15\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      before end of surgery. A total of six blood samples were drawn from each participant at the following time points: baseline, 0, 15, 30, 60, and 90\u2009min post\u2010injection. Plasma melatonin concentrations were determined with High\u2010Performance Liquid Chromatography with Fluorescence Detection (HPLC\u2010FLD). Pharmacokinetic parameters were estimated with non\u2010compartmental analysis. Clinical outcomes were recorded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 98 samples in the pharmacokinetic analysis. We found a maximum plasma concentration (\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) of 416\u2009298 [IQR 322\u2009230\u2013508\u2009006] pg\u00b7mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      and an elimination half\u2010life (\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      ) of 35.2 (SD 8.4) minutes. Clearance (CL) was 0.0183 (SD 0.0039) L\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      and volume of distribution (V\n                      <jats:sub>d<\/jats:sub>\n                      ) 0.92 (SD 0.27) L\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      . There were no cases of emergence delirium, mean maximum pain (FLACC) score was 1.3 (SD 2.0), and time to awakening and discharge readiness averaged one and two hours, respectively. Adverse events could be attributed to routine postoperative symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Administering intravenous melatonin in a dose of 0.15\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      in 1\u20136\u2010year\u2010olds yielded pharmacokinetic characteristics comparable to those reported in adults. The observed postoperative events were consistent with expected perioperative findings. These data support dose selection for trials investigating the perioperative use of melatonin in children.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      CTIS: EU CT 2024\u2010517592\u201020.\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>\n                      : NCT05541276 (registered 12\/09\u20102022)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pan.70248","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:56:52Z","timestamp":1782122212000},"page":"1308-1315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of Intravenous Melatonin in Preschool\u2010Aged Pediatric Surgical Patients"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-9946","authenticated-orcid":false,"given":"Anne Louise de Barros","family":"Garioud","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Juliane Marie Center Copenhagen University Hospital \u2013 Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-9715","authenticated-orcid":false,"given":"Arash","family":"Afshari","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Juliane Marie Center Copenhagen University Hospital \u2013 Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lau Romlund","family":"Halgreen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital, Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian \u00d8stergaard","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Glostrup Pharmacy  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-2560","authenticated-orcid":false,"given":"Lars Peter Kloster","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Anesthesiology Zealand University Hospital K\u00f8ge  K\u00f8ge Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/anae.12717"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181e7d626"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16011209"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010022\u201003149\u2010w"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-023-02356-x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-015-0368-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.51958"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-015-1873-4"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/aas.14342"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12092"},{"issue":"5","key":"e_1_2_12_12_1","first-page":"1882","article-title":"Pharmacokinetics 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