{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:37:05Z","timestamp":1790235425566,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T00:00:00Z","timestamp":1590019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV 001822"],"award-info":[{"award-number":["INV 001822"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>As chloroquine (CHQ) is part of the Dutch Centre for Infectious Disease Control coronavirus disease 2019 (COVID\u201019) experimental treatment guideline, pediatric dosing guidelines are needed. Recent pediatric data suggest that existing World Health Organization (WHO) dosing guidelines for children with malaria are suboptimal. The aim of our study was to establish best\u2010evidence to inform pediatric CHQ doses for children infected with COVID\u201019. A previously developed physiologically\u2010based pharmacokinetic (PBPK)\u00a0model for CHQ was used to simulate exposure in adults and children and verified against published pharmacokinetic data. The COVID\u201019 recommended adult dosage regimen of 44\u00a0mg\/kg total was tested in adults and children to evaluate the extent of variation in exposure. Based on differences in area under the concentration\u2010time curve from zero to 70 hours (AUC<jats:sub>0\u201370h<\/jats:sub>) the optimal CHQ dose was determined in children of different ages compared with adults. Revised doses were re\u2010introduced into the model to verify that overall CHQ exposure in each age band was within 5% of the predicted adult value. Simulations showed differences in drug exposure in children of different ages and adults when the same body\u2010weight based dose is given. As such, we propose the following total cumulative doses: 35\u00a0mg\/kg (CHQ base) for children 0\u20131\u00a0month, 47\u00a0mg\/kg for 1\u20136\u00a0months, 55\u00a0mg\/kg for 6\u00a0months\u201312\u00a0years, and 44\u00a0mg\/kg for adolescents and adults, not to exceed 3,300\u00a0mg in any patient. Our study supports age\u2010adjusted CHQ dosing in children with COVID\u201019 in order to avoid suboptimal or toxic doses. The knowledge\u2010driven, model\u2010informed dose selection paradigm can serve as a science\u2010based alternative to recommend pediatric dosing when pediatric clinical trial data is absent.<\/jats:p>","DOI":"10.1002\/cpt.1864","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T19:50:46Z","timestamp":1587585046000},"page":"248-252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Chloroquine Dosing Recommendations for Pediatric COVID\u201019 Supported by Modeling and Simulation"],"prefix":"10.1111","volume":"108","author":[{"given":"Laurens F. M.","family":"Verscheijden","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjitske M.","family":"van der Zanden","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Dutch Knowledge Center Pharmacotherapy for Children The Hague The Netherlands"},{"name":"Department of Paediatrics Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianne P. M.","family":"van Bussel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"de Hoop\u2010Sommen","sequence":"additional","affiliation":[{"name":"Dutch Knowledge Center Pharmacotherapy for Children The Hague The Netherlands"},{"name":"Royal Dutch Pharmacist Association The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G. M.","family":"Russel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor N.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Certara UK Limited Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia N.","family":"de Wildt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Dutch Knowledge Center Pharmacotherapy for Children The Hague The Netherlands"},{"name":"Intensive Care and Department of Paediatrics Surgery Erasmus MC\u2010Sophia Children's Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2005073"},{"key":"e_1_2_9_2_1","volume-title":"Request for Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease","author":"Hinton D.M.","year":"2020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00806-5"},{"key":"e_1_2_9_4_1","article-title":"In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102)","author":"Yao X.","journal-title":"Clin. Infect Dis."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0282-0"},{"key":"e_1_2_9_6_1","unstructured":"Vollaard A. Ellerbroek P. Gieling E. deBoer M. Snijder E.&vanDissel J.LCI richtlijn COVID\u201019. Bijlage Medicamenteuze behandelopties bij opgenomen pati\u00ebnten met COVID\u201019 wwwlcirivmnl(2020). [in Dutch]"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2016-311674"},{"key":"e_1_2_9_8_1","unstructured":"MEB.Summary of product characteristics chloroquine<https:\/\/www.geneesmiddeleninformatiebank.nl\/smpc\/h106659_smpc.pdf> (2018)."},{"key":"e_1_2_9_9_1","volume-title":"Guidelines for the Treatment of Malaria","author":"World Health Organization (WHO)","year":"2016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-36"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01846-19"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03050.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1284"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.33"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.539"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.10.033"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.905"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12101"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-014-9592-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00555-07"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1542\/peds.27.1.95","article-title":"Fatal acute chloroquine poisoning in children","volume":"27","author":"Cann H.M.","year":"1961","journal-title":"Pediatrics"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","unstructured":"Kelly J.C. Wasserman G.S. Bernard W.D. Schultz C.&Knapp J.Chloroquine poisoning in a child<https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/2297155> (1990).","DOI":"10.1016\/S0196-0644(05)82141-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq001"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-015-1164-y"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1864","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1864","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1864","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:37:46Z","timestamp":1699364266000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,21]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/cpt.1864"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1864","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,21]]},"assertion":[{"value":"2020-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}