Repurposing Drugs for COVID-19: Pharmacokinetics and Pharmacogenomics of Chloroquine and Hydroxychloroquine

BACKGROUND: A new coronavirus SARS-CoV-2 has been identified as the etiological agent of the severe acute respiratory syndrome, COVID-19, the source and cause of the 2019–20 coronavirus pandemic. Hydroxychloroquine and chloroquine have gathered extraordinary attention as therapeutic candidates against SARS-CoV-2 infections. While there is growing scientific data on the therapeutic effect, there is also concern for toxicity of the medications. The therapy of COVID-19 by hydroxychloroquine and chloroquine is off-label. Studies to analyze the personalized effect and safety are lacking. METHODS: A review of the literature was performed using Medline/PubMed/Embase database. A variety of keywords were employed in keyword/title/abstract searches. The electronic search was followed by extensive hand searching using reference lists from the identified articles. RESULTS: A total of 126 results were obtained after screening all sources. Mechanisms underlying variability in drug concentrations and therapeutic response with chloroquine and hydroxychloroquine in mediating beneficial and adverse effects of chloroquine and hydroxychloroquine were reviewed and analyzed. Pharmacogenomic studies from various disease states were evaluated to elucidate the role of genetic variation in drug response and toxicity. CONCLUSION: Knowledge of the pharmacokinetics and pharmacogenomics of chloroquine and hydroxychloroquine is necessary for effective and safe dosing and to avoid treatment failure and severe complications.