{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:59:07Z","timestamp":1765976347659},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08 AI134262","R01AI140303","U01AI125003"],"award-info":[{"award-number":["K08 AI134262","R01AI140303","U01AI125003"]}],"id":[{"id":"10.13039\/100000060","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":[[2020,10]]},"abstract":"<jats:p>Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID\u201019) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID\u201019 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the <jats:italic>in vitro<\/jats:italic> generated half maximal effective concentration (EC<jats:sub>50<\/jats:sub>) and to help guide researchers in dose\u2010selection for COVID\u201019 prophylactic studies. To maintain weekly troughs above EC<jats:sub>50<\/jats:sub> in &gt;\u00a050% of subjects at steady\u2010state in a pre\u2010exposure prophylaxis setting, an 800\u00a0mg loading dose followed by 400\u00a0mg twice or 3 times weekly is required. In an exposure driven, post\u2010exposure prophylaxis setting, 800\u00a0mg loading dose followed in 6\u00a0hours by 600\u00a0mg, then 600\u00a0mg daily for 4 more days achieved daily troughs above EC<jats:sub>50<\/jats:sub> in &gt;\u00a050% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.<\/jats:p>","DOI":"10.1002\/cpt.1874","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T21:04:11Z","timestamp":1588107851000},"page":"766-769","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Finding the Dose for Hydroxychloroquine Prophylaxis for COVID\u201019: The Desperate Search for Effectiveness"],"prefix":"10.1111","volume":"108","author":[{"given":"Mahmoud","family":"Al\u2010Kofahi","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamala","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur","family":"Matas","sequence":"additional","affiliation":[{"name":"Department of Surgery Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raja","family":"Kandaswamy","sequence":"additional","affiliation":[{"name":"Department of Surgery Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutaz M.","family":"Jaber","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radha","family":"Rajasingham","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u2010Anne H.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie R.","family":"Nicol","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2020.01012"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0156-0"},{"key":"e_1_2_9_3_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_4_1","article-title":"Towards optimization of hydroxychloroquine dosing in intensive care unit COVID\u201019 patients","author":"Perinel S.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1856"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00339-08"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203317727601"},{"key":"e_1_2_9_8_1","unstructured":"Report of the WHO\u2010China Joint Mission on Coronavirus Disease 2019 (COVID\u201019). <https:\/\/www.who.int\/docs\/default\u2010source\/coronaviruse\/who\u2010china\u2010joint\u2010mission\u2010on\u2010covid\u201019\u2010final\u2010report.pdf> (2020)."},{"key":"e_1_2_9_9_1","article-title":"A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease\u201019 (COVID\u201019)","author":"Chen J.","journal-title":"J. Zhejiang Univ. (Med. 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