{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:41Z","timestamp":1772160101589,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) is a newly identified pathogen causing the coronavirus disease 2019 (COVID\u201019) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti\u2010inflammatory drug, has been shown to inhibit SARS\u2010CoV\u20102 infection\n                    <jats:italic>in vitro<\/jats:italic>\n                    and tested in clinical studies. However, achievement of lung concentrations predicted to have\n                    <jats:italic>in vivo<\/jats:italic>\n                    antiviral efficacy might not be possible with the currently proposed oral dosing regimens. Further, high cumulative doses of HCQ raise concerns of systemic toxicity, including cardiotoxicity. Here, we describe a preclinical study to investigate the pharmacokinetics (PKs) of a novel formulation of liposomal HCQ administered by intratracheal (IT) instillation in Sprague\u2010Dawley rats. Compared with unformulated HCQ administered intravenously, liposomal HCQ showed higher (~\u00a030\u2010fold) lung exposure, longer (~\u00a02.5\u2010fold) half\u2010life in lungs, but lower blood exposure with ~\u00a020% of peak plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) and 74% of area under the curve from 0 to 72 hours (AUC\n                    <jats:sub>0\u201372<\/jats:sub>\n                    ) and lower heart exposure with 23% of C\n                    <jats:sub>max<\/jats:sub>\n                    and 58% of AUC\n                    <jats:sub>0\u201324<\/jats:sub>\n                    (normalized for dose). Similar results were observed relative to IT administration of unformulated HCQ. These PKs result in an animal model that demonstrated the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID\u201019.\n                  <\/jats:p>","DOI":"10.1111\/cts.12923","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T03:38:18Z","timestamp":1604288298000},"page":"132-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A Strategy to Treat COVID\u201019 Disease With Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Preclinical Pharmacokinetic Study"],"prefix":"10.1111","volume":"14","author":[{"given":"Tien\u2010Tzu","family":"Tai","sequence":"first","affiliation":[{"name":"Division of Corporate Development Department of Regulatory Affairs Taiwan Liposome Company, Ltd.  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzung\u2010Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Product Development Department of Pharmacokinetics Taiwan Liposome Company, Ltd.  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huey\u2010Dong","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Respiratory Therapy Department of Integrated Diagnostics and Therapeutics National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Chen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Product Development Department of Pharmacokinetics Taiwan Liposome Company, Ltd.  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Product Development Department of Pharmacokinetics Taiwan Liposome Company, Ltd.  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An\u2010Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Product Development Department of Medical Science Taiwan Liposome Company, Ltd.  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheue\u2010Fang","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Product Development Taiwan Liposome Company, Ltd.  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yee\u2010Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Infectious disease Department of Internal Medicine National Taiwan University Hospital and College of Medicine  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.15.166"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0156-0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa237"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.105949"},{"key":"e_1_2_10_5_1","article-title":"Efficacy of hydroxychloroquine in patients with COVID\u201019: results of a randomized clinical trial","author":"Chen Z.","journal-title":"medRxiv"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2016638"},{"key":"e_1_2_10_7_1","article-title":"Hydroxychloroquine with or without azithromycin in mild\u2010to\u2010moderate Covid\u201019","author":"Cavalcanti A.B.","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_10_8_1","article-title":"Connecting hydroxychloroquine in vitro antiviral activity to in vivo concentration for prediction of antiviral effect: a critical step in treating COVID\u201019 patients","author":"Fan J.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_2_10_9_1","article-title":"Hydroxychloroquine for treatment of SARS\u2010CoV\u20102 infection? Improving our confidence in a model\u2010based approach to dose selection","author":"Arnold S.L.M.","journal-title":"Clin. Transl. Sci."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0372-x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2017.11.026"},{"key":"e_1_2_10_12_1","first-page":"429","article-title":"Development of an inhaled hydroxychloroquine sulfate product using the AERx system to treat asthma","author":"Dayton F.","year":"2006","journal-title":"Respir. Drug Deliv."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01095-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa191"},{"key":"e_1_2_10_15_1","unstructured":"US Food and Drug Administration (FDA).FDA cautions against use of hydroxychloroquine or chloroquine for COVID\u201019 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems.FDA Drug Safety Communication<https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/fda\u2010cautions\u2010against\u2010use\u2010hydroxychloroquine\u2010or\u2010chloroquine\u2010covid\u201019\u2010outside\u2010hospital\u2010setting\u2010or> (2020)."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.109783"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.110110"},{"key":"e_1_2_10_18_1","unstructured":"Centers for Disease Control and Prevention (CDC).National Center for Immunization and Respiratory Diseases (NCIRD) Division of Viral Diseases Interim Infection Prevention and Control Recommendations for Healthcare Personnel During the Coronavirus Disease 2019 (COVID\u201019) Pandemic<https:\/\/www.cdc.gov\/coronavirus\/2019\u2010ncov\/hcp\/infection\u2010control\u2010recommendations.html>."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12923","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12923","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12923","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T02:09:57Z","timestamp":1693620597000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/cts.12923"],"URL":"https:\/\/doi.org\/10.1111\/cts.12923","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.09.196618","asserted-by":"object"}]},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]},"assertion":[{"value":"2020-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}