{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:47Z","timestamp":1786977527698,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","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>\n                    Azithromycin (AZ) is a broad\u2010spectrum macrolide antibiotic with a long half\u2010life and a large volume of distribution. It is primarily used for the treatment of respiratory, enteric, and genitourinary bacterial infections. AZ is not approved for the treatment of viral infections, and there is no well\u2010controlled, prospective, randomized clinical evidence to support AZ therapy in coronavirus disease 2019 (COVID\u201019). Nevertheless, there are anecdotal reports that some hospitals have begun to include AZ in combination with hydroxychloroquine or chloroquine (CQ) for treatment of COVID\u201019. It is essential that the clinical pharmacology (CP) characteristics of AZ be considered in planning and conducting clinical trials of AZ alone or in combination with other agents, to ensure safe study conduct and to increase the probability of achieving definitive answers regarding efficacy of AZ in the treatment of COVID\u201019. The safety profile of AZ used as an antibacterial agent is well established.\n                    <jats:sup>1<\/jats:sup>\n                    This work assesses published\n                    <jats:italic>in vitro<\/jats:italic>\n                    and clinical evidence for AZ as an agent with antiviral properties. It also provides basic CP information relevant for planning and initiating COVID\u201019 clinical studies with AZ, summarizes safety data from healthy volunteer studies, and safety and efficacy data from phase II and phase II\/III studies in patients with uncomplicated malaria, including a phase II\/III study in pediatric patients following administration of AZ and CQ in combination. This paper may also serve to facilitate the consideration and use of\n                    <jats:italic>a priori<\/jats:italic>\n                    \u2013defined control groups for future research.\n                  <\/jats:p>","DOI":"10.1002\/cpt.1857","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T13:54:45Z","timestamp":1587131685000},"page":"201-211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["Clinical Pharmacology Perspectives on the Antiviral Activity of Azithromycin and Use in COVID\u201019"],"prefix":"10.1111","volume":"108","author":[{"given":"Bharat","family":"Damle","sequence":"first","affiliation":[{"name":"Pfizer Global Research and Development New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoli","family":"Vourvahis","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erjian","family":"Wang","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Leaney","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development Sandwich Kent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Corrigan","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"ZITHROMAX [package insert]. (Pfizer New York NY 2020)."},{"key":"e_1_2_7_2_1","article-title":"Hydroxychloroquine and azithromycin as a treatment of COVID\u201019: results of an open\u2010label non\u2010randomized clinical trial","author":"Gautret P.","journal-title":"Int. J. Antimicrob. Agents"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","unstructured":"Gautret P.et al.Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID\u201019 patients with at least a six\u2010day follow up: an observational study<https:\/\/www.mediterranee\u2010infection.com\/wp\u2010content\/uploads\/2020\/03\/COVID\u2010IHU\u20102\u20101.pdf> (2020).","DOI":"10.1016\/j.tmaid.2020.101663"},{"key":"e_1_2_7_4_1","article-title":"In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS\u2010CoV\u20102 replication","author":"Touret F.","journal-title":"bioRxiv"},{"key":"e_1_2_7_5_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_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0156-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","unstructured":"Andreania J.et al.In vitro testing of Hydroxychloroquine and Azithromycin on SARS\u2010CoV\u20102 shows synergistic effect<https:\/\/www.mediterranee\u2010infection.com\/wp\u2010content\/uploads\/2020\/03\/La\u2010Scola\u2010et\u2010al\u2010V1.pdf> (2020).","DOI":"10.1016\/j.micpath.2020.104228"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00394-19"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618029113"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2014.88"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.11.065"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00030"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-019-0204-x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00095809"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2002.5613"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","unstructured":"Homolak J.&Kodvanj I.Widely available lysosome targeting agents should be considered as a potential therapy for COVID\u201019. Preprints 2020 https:\/\/doi.org\/10.20944\/preprints202003.0345.v2.","DOI":"10.20944\/preprints202003.0345.v2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(94)90126-0"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28698"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2017.1285677"},{"key":"e_1_2_7_20_1","article-title":"Energetics based modeling of hydroxychloroquine and azithromycin binding to the SARS\u2010CoV\u20102 spike (S) protein \u2013 ACE2 complex","author":"Sandeep S.","journal-title":"ChemRxiv"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.17299"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00852-06"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043661802002384"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg138"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn032"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02011-12"},{"key":"e_1_2_7_27_1","article-title":"No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID\u201019 infection","author":"Molina J.M.","journal-title":"Med Mal. Infect."},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2019.01.041"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.05320-0"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091293"},{"key":"e_1_2_7_31_1","article-title":"Assessment of efficacy of Oseltamivir\u2010Azithromycin combination therapy in prevention of Influenza\u2010A (H1N1)pdm09 infection complications and rapidity of symptoms relief","author":"Ishaqui A.A.","journal-title":"Expert Rev. Respir. Med."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.10.001"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.12.020"},{"key":"e_1_2_7_34_1","unstructured":"Plaquenil[package insert]. (Concordia Pharmaceuticals St Michael Barbados 2015)."},{"key":"e_1_2_7_35_1","unstructured":"Aralen[package insert]. (Sanofi\u2010Aventis Bridgewater NJ 2013)."},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.74.407"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.034629"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0954-6820.1982.tb01971.x"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127000004001226"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.809-814.2004"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02976712"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2000.00197.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(01)80049-7"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(67)90089-0"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1076"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31281-3"},{"key":"e_1_2_7_47_1","doi-asserted-by":"crossref","unstructured":"Chorin E.et al.The QT Interval in Patients with SARS\u2010CoV\u20102 Infection Treated with Hydroxychloroquine\/Azithromycin. medRxiv https:\/\/doi.org\/10.1101\/2020.04.02.20047050.","DOI":"10.1101\/2020.04.02.20047050"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1857","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1857","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T08:37:45Z","timestamp":1699346265000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,12]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/cpt.1857"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1857","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,12]]},"assertion":[{"value":"2020-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}