{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:58:44Z","timestamp":1770040724244,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T00:00:00Z","timestamp":1477353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000148","name":"Canadian Anesthesiologists' Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000148","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Oral morphine has been proposed as an effective and safe alternative to codeine for after\u2010discharge pain in children following surgery but there are few data guiding an optimum safe oral dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The aim of this study was to characterize the absorption pharmacokinetics of enteral morphine in order to simulate time\u2013concentration profiles in children given common oral morphine dose regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Children (2\u20136 years, <jats:italic>n<\/jats:italic> = 34) undergoing elective surgery and requiring opioid analgesia were randomized to receive preoperative oral morphine (100 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup>, 200 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup>, 300 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup>). Blood sampling for morphine assay was performed at 30, 60, 90, 120, 180, and 240 min. Morphine serum concentrations were determined by liquid chromatography\u2013mass spectroscopy and pharmacokinetic parameters were calculated using nonlinear mixed effects models. Current data were pooled with published time\u2013concentration profiles from children (<jats:italic>n<\/jats:italic> = 1059, age 23 weeks postmenstrual age \u2013 3 years) administered intravenous morphine, to determine oral bioavailability (F), absorption lag time (T<jats:sub>LAG<\/jats:sub>), and absorption half\u2010time (T<jats:sub>ABS<\/jats:sub>). These parameter estimates were used to predict concentrations in children given oral morphine (100, 200, 300, 400, 500 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup>) at different dosing intervals (3, 4, 5, 6, 8, 12 h).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The oral morphine formulation had F 0.298 (CV 36.5%), T<jats:sub>LAG<\/jats:sub> 0.45 (CV 63.6%) h and T<jats:sub>ABS<\/jats:sub> 0.71 (CV 55%) h. A single\u2010dose morphine 100 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup> achieved a mean C<jats:sub>MAX<\/jats:sub> 10 mcg\u00b7l<jats:sup>\u22121<\/jats:sup>. Repeat 4\u2010hourly dosing achieved mean steady\u2010state concentration 13\u201318 mcg\u00b7l<jats:sup>\u22121<\/jats:sup>; concentrations associated with good analgesia after intravenous administration. Serum concentration variability was large ranging from 5 to 55 mcg\u00b7l<jats:sup>\u22121<\/jats:sup> at steady state.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Oral morphine 200 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup> then 100 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup> 4 h or 150 mcg\u00b7kg<jats:sup>\u22121<\/jats:sup> 6 h achieves mean concentrations associated with analgesia. There was high serum concentration variability suggesting that respiration may be compromised in some children given these doses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.13020","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T12:13:07Z","timestamp":1477397587000},"page":"28-36","source":"Crossref","is-referenced-by-count":29,"title":["Oral morphine dosing predictions based on single dose in healthy children undergoing surgery"],"prefix":"10.1111","volume":"27","author":[{"given":"Joy M.","family":"Dawes","sequence":"first","affiliation":[{"name":"Department of Anaesthesia Great Ormond Street Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin M.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline A.","family":"Hannam","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology School of Medicine University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine A.","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia Evelina London Children's Hospital and St Thomas' Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Winton","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia Royal Hospital for Sick Children Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Jimenez\u2010Mendez","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Faculty of Medicine University of British Columbia Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina","family":"Aleksa","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology\/Toxicology Hospital for Sick Children Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian R.","family":"Lauder","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce C.","family":"Carleton","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Faculty of Medicine University of British Columbia Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gideon","family":"Koren","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology\/Toxicology Hospital for Sick Children Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Rieder","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics University of Western Ontario London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology School of Medicine University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyne J.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-2538"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aes447"},{"key":"e_1_2_9_4_1","unstructured":"MHRA.Codeine for analgesia: restricted use in children because of reports of morphine toxicity2013. 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