Predictions of Systemic, Intracellular, and Lung Concentrations of Azithromycin with Different Dosing Regimens used in COVID ‐19 Clinical Trials

AbstractAzithromycin, a broad ‐spectrum macrolide antibiotic, is being investigated in patients with COVID‐19. A population pharmacokinetic model was implemented to predict lung, intracellular poly/mononuclear cell (PBM/PML), and alveolar macrophage (AM) concentrations using published data and compared against preclinical EC 90 for SARS‐CoV‐2. The final model described the data reported in 8 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 do se and for approximately 14 days following 500 mg QD for 3 days or 500 mg QD for 1 day/250 mg QD on days 2‐5, 10 days following a single 1000 mg dose, and for more than 20 days with 500 mg QD for 10 days. AM concentrations exceeded the IC90 for more than 20 days for all regimens. These data will b etter inform optimization of dosing regimens for azithromycin clinical trials.
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research