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10.1007/s10928-020-09690-4

http://scihub22266oqcxt.onion/10.1007/s10928-020-09690-4
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suck abstract from ncbi

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  • Model based approach for estimating the dosage regimen of indomethacin a potential antiviral treatment of patients infected with SARS CoV-2 #MMPMID32435882
  • Gomeni R; Xu T; Gao X; Bressolle-Gomeni F
  • J Pharmacokinet Pharmacodyn 2020[Jun]; 47 (3): 189-198 PMID32435882show ga
  • To face SARS-CoV-2 pandemic various attempts are made to identify potential effective treatments by repurposing available drugs. Among them, indomethacin, an anti-inflammatory drug, was shown to have potent in-vitro antiviral properties on human SARS-CoV-1, canine CCoV, and more recently on human SARS-CoV-2 at low micromolar range. Our objective was to show that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 and to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. A multi-stage model-based approach was developed to characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indomethacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human. Different dosage regimens were evaluated for IR formulation (25 mg and 50 mg three-times-a-day, and 25 mg four-times-a-day), and SR formulation (75 mg once and twice-a-day). The best performing dosing regimens were: 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation. The treatment with the SR formulation at the dose of 75 mg twice-a-day is expected to achieve a complete response in three days for the treatment in patients infected by the SARS-CoV-2 coronavirus. These results suggest that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 whose potential therapeutic effect need to be further assessed in a prospective clinical trial.
  • |*Drug Dosage Calculations[MESH]
  • |*Models, Biological[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*administration & dosage/pharmacokinetics/*therapeutic use[MESH]
  • |Betacoronavirus/drug effects[MESH]
  • |Coronavirus Infections/*drug therapy/virology[MESH]
  • |Delayed-Action Preparations/administration & dosage/pharmacokinetics/therapeutic use[MESH]
  • |Dogs[MESH]
  • |Humans[MESH]
  • |Indomethacin/*administration & dosage/pharmacokinetics/*therapeutic use[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*drug therapy/virology[MESH]
  • |Viral Load/drug effects[MESH]


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  • suck abstract from ncbi

    189 3.47 2020