Article ; Online: Predictions of Systemic, Intracellular, and Lung Concentrations of Azithromycin With Different Dosing Regimens Used in COVID‐19 Clinical Trials
CPT: Pharmacometrics & Systems Pharmacology, Vol 9, Iss 8, Pp 435-
2020 Volume 443
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 ... ...
| 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. |
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| Keywords | Therapeutics. Pharmacology ; RM1-950 ; covid19 |
| Subject code | 610 |
| Language | English |
| Publishing date | 2020-08-01T00:00:00Z |
| Publisher | Wiley |
| Document type | Article ; Online |
| Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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