Open AccessPredictions of Systemic, Intracellular, and Lung Concentrations of Azithromycin With Different Dosing Regimens Used in COVID‐19 Clinical Trials
Author(s) -
Hughes Jim H.,
Sweeney Kevin,
Ahadieh Sima,
Ouellet Daniele
Publication year - 2020
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12537
Subject(s) - azithromycin , dosing , medicine , peripheral blood mononuclear cell , pharmacology , pharmacokinetics , population , covid-19 , lung , respiratory system , clinical trial , antibiotics , gastroenterology , chemistry , biology , microbiology and biotechnology , in vitro , disease , biochemistry , environmental health , infectious disease (medical specialty)
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% (EC 90 ) 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 EC 90 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.