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.