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10.1093/cid/ciaa237

http://scihub22266oqcxt.onion/10.1093/cid/ciaa237
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32150618!7108130!32150618
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suck abstract from ncbi


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pmid32150618      Clin+Infect+Dis 2020 ; 71 (15): 732-739
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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) #MMPMID32150618
  • Yao X; Ye F; Zhang M; Cui C; Huang B; Niu P; Liu X; Zhao L; Dong E; Song C; Zhan S; Lu R; Li H; Tan W; Liu D
  • Clin Infect Dis 2020[Jul]; 71 (15): 732-739 PMID32150618show ga
  • 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 muM) was found to be more potent than chloroquine (EC50 = 5.47 muM) 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.
  • |Animals[MESH]
  • |Antiviral Agents/pharmacokinetics/*pharmacology[MESH]
  • |Betacoronavirus/*drug effects[MESH]
  • |COVID-19[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Chloroquine/pharmacokinetics/pharmacology[MESH]
  • |Coronavirus Infections/*drug therapy[MESH]
  • |Hydroxychloroquine/pharmacokinetics/*pharmacology[MESH]
  • |Lung/drug effects[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*drug therapy[MESH]
  • |SARS-CoV-2[MESH]
  • |Severe Acute Respiratory Syndrome/*drug therapy[MESH]


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