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

ABSTRACT: 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.

SUBMITTER: Babayeva M

PROVIDER: S-EPMC7591012 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Babayeva Mariana M Loewy Zvi Z

Pharmacogenomics and personalized medicine 20201023

<h4>Background</h4>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 ...[more]

PMID: 33122936

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Project description:IntroductionGiven the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug.BackgroundThe in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis.Review resultsLiterature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes.ConclusionAs per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia.How to cite this articleShetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.

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

Publications

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

Similar Datasets

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