Clinical Pharmacokinetics and Pharmacodynamics data extraction of COVID-19 repurposed compounds and COVID-19 patient characteristics
Trials of drugs repurposed for COVID-19 were selected in this work from the American Society of Health-System Pharmacists (ASHP) list [15]. In addition, two drugs from AstraZeneca currently being studied in clinical trials are acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor [3], and dapagliflozin, a sodium-glucose transport protein 2 (SGLT2) inhibitor. Details of these and other repurposed drugs are summarized in detail in Table 1 and in Supplementary Text. These repurposed drugs were anti-virals (azithromycin, atazanavir, baloxavir, darunavir, lopinavir, remdesivir, ritonavir), anti-cancer drugs (acalabrutinib, baricitinib, ruxolitinib), anti-inflammatory and immunomodulators (dexamethasone), biologicals (siltuximab, emapalumab, tocilizumab), antimalarial (chloroquine, hydroxychloroquine), and anti-diabetic and heart failure treatment drug (dapagliflozin). Clinical studies for probe compounds were queried with appropriate literature searches and through the University of Washington Drug Interaction Database (UWDIDB). Dosing regimens, relevant PK parameters, DDI, adverse events, applicable demographic data, such as age, gender, race, PK in hepatic and renal impairment and genotype, were manually extracted from the selected publications. Cytokine information, such as IL-6 levels in a typical COVID-19 patient, was extracted from literature and compared with other cytokine storm disease conditions such as cancer, rheumatoid arthritis etc.