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Home   COVID-19 treatment studies for Hydroxychloroquine  COVID-19 treatment studies for HCQ  C19 studies: HCQ  HCQ   Select treatmentSelect treatmentTreatmentsTreatments
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In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (In Vitro)
Yao et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment.., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (In Vitro)
Mar 2020   Source   PDF  
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In Vitro study showing that HCQ is more potent than CQ in vitro for inhibiting SARS-CoV-2. Simulates HCQ concentration in lung fluid and provides dosing recommendations.
See also [academic.oup.com, sciencedirect.com].
14 In Vitro studies support the efficacy of HCQ [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].
Yao et al., 9 Mar 2020, peer-reviewed, 16 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Abstract: Clinical Infectious Diseases MAJOR ARTICLE In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Xueting Yao,1,a Fei Ye,2,a Miao Zhang,1,a Cheng Cui,1,a Baoying Huang,2,a Peihua Niu,2 Xu Liu,1 Li Zhao,2 Erdan Dong,3 Chunli Song,4 Siyan Zhan,5 Roujian Lu,2 Haiyan Li,1,3,b Wenjie Tan,2,b and Dongyang Liu1,b Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China, 2NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China, 3Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China, 4Department of Orthopedics, Peking University Third Hospital, Beijing, China, and 5Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China Background. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods. The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug’s safety profile. Results. Hydroxychloroquine (EC50 = 0.72 μM) was found to be more potent than chloroquine (EC50 = 5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Conclusions. Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro. Keywords. chloroquine; hydroxychloroquine; SARS-CoV-2. In December 2019 the outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-2019), was first reported in Wuhan, China. The outbreak has since rapidly spread to other provinces in mainland China, as well as other countries around the world. Currently, the number of people diagnosed with SARS-CoV-2 infection is increasing by approximately 1000 cases per day. Unfortunately, to date, no drugs have been approved by regulatory agencies for the treatment of SARS-CoV-2 infection. Received 25 February 2020; editorial decision 2 March 2020; accepted 12 March 2020; published online March 9, 2020. a X. Y., F. Y., M. Z., C. C., and B. H. contributed equally to this work. b D. L., W. T., and H. L. contributed equally to this work. Correspondence: D. Liu,..
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