Predictions of Systemic, Intracellular, and Lung Concentrations of Azithromycin With Different Dosing Regimens Used in COVID-19 Clinical Trials.
CPT Pharmacometrics Syst Pharmacol
; 9(8): 435-443, 2020 08.
Article
in English
| MEDLINE | ID: covidwho-574626
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Coronavirus Infections
/
Azithromycin
/
Anti-Bacterial Agents
Type of study:
Prognostic study
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
CPT Pharmacometrics Syst Pharmacol
Year:
2020
Document Type:
Article
Affiliation country:
Psp4.12537
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