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10.1002/psp4.12537

http://scihub22266oqcxt.onion/10.1002/psp4.12537
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32511867!7300789!32511867
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suck abstract from ncbi

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  • Predictions of Systemic, Intracellular, and Lung Concentrations of Azithromycin With Different Dosing Regimens Used in COVID-19 Clinical Trials #MMPMID32511867
  • Hughes JH; Sweeney K; Ahadieh S; Ouellet D
  • CPT Pharmacometrics Syst Pharmacol 2020[Aug]; 9 (8): 435-443 PMID32511867show ga
  • Azithromycin (AZ), a broad-spectrum macrolide antibiotic, is being investigated in patients with coronavirus disease 2019 (COVID-19). A population pharmacokinetic model was implemented to predict lung, intracellular poly/mononuclear cell (peripheral blood monocyte (PBM)/polymorphonuclear leukocyte (PML)), and alveolar macrophage (AM) concentrations using published data and compared against preclinical effective concentration 90% (EC90 ) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The final model described the data reported in eight publications adequately. Consistent with its known properties, concentrations were higher in AM and PBM/PML, followed by lung tissue, and lowest systemically. Simulated PBM/PML concentrations exceeded EC90 following the first dose and for ~ 14 days following 500 mg q.d. for 3 days or 500 mg q.d. for 1 day/250 mg q.d. on days 2-5, 10 days following a single 1,000 mg dose, and for > 20 days with 500 mg q.d. for 10 days. AM concentrations exceeded the 90% inhibitory concentration for > 20 days for all regimens. These data will better inform optimization of dosing regimens for AZ clinical trials.
  • |Anti-Bacterial Agents/*administration & dosage/pharmacokinetics[MESH]
  • |Azithromycin/*administration & dosage/pharmacokinetics[MESH]
  • |Coronavirus Infections/*drug therapy[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |Humans[MESH]
  • |Leukocytes, Mononuclear/metabolism[MESH]
  • |Lung/metabolism[MESH]
  • |Macrophages, Alveolar/metabolism[MESH]
  • |Models, Biological[MESH]
  • |Neutrophils/metabolism[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*drug therapy[MESH]
  • |Tissue Distribution[MESH]


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  • suck abstract from ncbi

    435 8.9 2020