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Antiviral Research May 2020Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel... (Review)
Review
Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; China; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32147496
DOI: 10.1016/j.antiviral.2020.104762 -
Medecine Et Maladies Infectieuses May 2020
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Chloroquine; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Failure
PubMed: 32217166
DOI: 10.1016/j.medmal.2020.03.004 -
Molecules (Basel, Switzerland) Dec 2020The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use... (Review)
Review
The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.
Topics: Animals; Antimalarials; Chloroquine; Communicable Diseases; Drug Compounding; Humans; Hydroxychloroquine; Nanomedicine
PubMed: 33396545
DOI: 10.3390/molecules26010175 -
Journal of Medical Toxicology :... Jul 2020SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is causing the COVID-19 pandemic. There is no current standard of care. Clinicians need to be mindful of the... (Review)
Review
SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is causing the COVID-19 pandemic. There is no current standard of care. Clinicians need to be mindful of the toxicity of a wide variety of possibly unfamiliar substances being tested or repurposed to treat COVID-19. The United States Food and Drug Administration (FDA) has provided emergency authorization for the use of chloroquine and hydroxychloroquine. These two medications may precipitate ventricular dysrhythmias, necessitating cardiac and electrolyte monitoring, and in severe cases, treatment with epinephrine and high-doses of diazepam. Recombinant protein therapeutics may cause serum sickness or immune complex deposition. Nucleic acid vaccines may introduce mutations into the human genome. ACE inhibitors and ibuprofen have been suggested to exacerbate the pathogenesis of COVID-19. Here, we review the use, mechanism of action, and toxicity of proposed COVID-19 therapeutics.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Chloroquine; Coronavirus Infections; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; United States
PubMed: 32356252
DOI: 10.1007/s13181-020-00777-5 -
Archives of Pharmacal Research Aug 2020A novel coronavirus, later named SARS-CoV-2, was first reported in China in December 2019 and subsequently widely identified in the United States, Japan, South Korea,... (Review)
Review
A novel coronavirus, later named SARS-CoV-2, was first reported in China in December 2019 and subsequently widely identified in the United States, Japan, South Korea, France, India, and other countries. The disease caused by SARS-CoV-2 infection was called COVID-19. The high fatality and morbidity rates of COVID-19 make it the third largest global epidemic in this century. However, there are currently no approved antiviral drugs for the COVID-19 treatment. Recently, two old antimalarial drugs, hydroxychloroquine and chloroquine, have been found to exert anti-SARS-CoV-2 effects both in vitro and in vivo. Preliminary clinical evidence suggests these drugs may have an effect on the treatment of COVID-19. Herein, we review the pharmacokinetics characteristics and antiviral effects of these drugs, in addition to their side effects and clinical evidence of their use for the COVID-19 treatment.
Topics: Antimalarials; COVID-19; Chloroquine; Coronavirus Infections; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; COVID-19 Drug Treatment
PubMed: 32740801
DOI: 10.1007/s12272-020-01258-7 -
American Journal of Ophthalmology May 2020
Topics: Antiviral Agents; COVID-19; Chloroquine; Coronavirus Infections; Dose-Response Relationship, Drug; Humans; Hydroxychloroquine; Ophthalmology; Pandemics; Pneumonia, Viral; Retina
PubMed: 32247518
DOI: 10.1016/j.ajo.2020.03.028 -
Clinical Pharmacology and Therapeutics Dec 2020Chloroquine and hydroxychloroquine are quinoline derivatives used to treat malaria. To date, these medications are not approved for the treatment of viral infections,... (Review)
Review
Chloroquine and hydroxychloroquine are quinoline derivatives used to treat malaria. To date, these medications are not approved for the treatment of viral infections, and there are no well-controlled, prospective, randomized clinical studies or evidence to support their use in patients with coronavirus disease 2019 (COVID-19). Nevertheless, chloroquine and hydroxychloroquine are being studied alone or in combination with other agents to assess their effectiveness in the treatment or prophylaxis for COVID-19. The effective use of any medication involves an understanding of its pharmacokinetics, safety, and mechanism of action. This work provides basic clinical pharmacology information relevant for planning and initiating COVID-19 clinical studies with chloroquine or hydroxychloroquine, summarizes safety data from healthy volunteer studies, and summarizes safety data from phase II and phase II/III clinical studies in patients with uncomplicated malaria, including a phase II/III study in pediatric patients following administration of azithromycin and chloroquine in combination. In addition, this work presents data describing the proposed mechanisms of action against the severe acute respiratory distress syndrome coronavirus-2 and summarizes clinical efficacy to date.
Topics: Age Factors; Aging; Antiviral Agents; Chloroquine; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Interactions; Drug Therapy, Combination; Humans; Hydroxychloroquine; Liver Failure; Malaria; Prospective Studies; Renal Insufficiency; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32687630
DOI: 10.1002/cpt.1993 -
The Western Journal of Emergency... Jun 2020As of April 21, 2020, more than 2.5 million cases of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, have been reported in 210 countries and... (Review)
Review
As of April 21, 2020, more than 2.5 million cases of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, have been reported in 210 countries and territories, with the death toll at 171,810. Both chloroquine and hydroxychloroquine have gained considerable media attention as possible therapies, resulting in a significant surge in demand. In overdose, both medications can cause severe, potentially life-threatening effects. Here, we present a brief overview of the pharmacology of chloroquine and hydroxychloroquine, manifestations of toxicity, and treatment considerations.
Topics: Betacoronavirus; COVID-19; Chloroquine; Coronavirus Infections; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32726238
DOI: 10.5811/westjem.2020.5.47810 -
Current Drug Metabolism 2020In clinical practice, chloroquine and hydroxychloroquine are often co-administered with other drugs in the treatment of malaria, chronic inflammatory diseases, and... (Review)
Review
BACKGROUND
In clinical practice, chloroquine and hydroxychloroquine are often co-administered with other drugs in the treatment of malaria, chronic inflammatory diseases, and COVID-19. Therefore, their metabolic properties and the effects on the activity of cytochrome P450 (P450, CYP) enzymes and drug transporters should be considered when developing the most efficient treatments for patients.
METHODS
Scientific literature on the interactions of chloroquine and hydroxychloroquine with human P450 enzymes and drug transporters, was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/) and the ADME database (https://life-science.kyushu.fujitsu.com/admedb/).
RESULTS
Chloroquine and hydroxychloroquine are metabolized by P450 1A2, 2C8, 2C19, 2D6, and 3A4/5 in vitro and by P450s 2C8 and 3A4/5 in vivo by N-deethylation. Chloroquine effectively inhibited P450 2D6 in vitro; however, in vivo inhibition was not apparent except in individuals with limited P450 2D6 activity. Chloroquine is both an inhibitor and inducer of the transporter MRP1 and is also a substrate of the Mate and MRP1 transport systems. Hydroxychloroquine also inhibited P450 2D6 and the transporter OATP1A2.
CONCLUSIONS
Chloroquine caused a statistically significant decrease in P450 2D6 activity in vitro and in vivo, also inhibiting its own metabolism by the enzyme. The inhibition indicates a potential for clinical drug-drug interactions when taken with other drugs that are predominant substrates of the P450 2D6. When chloroquine and hydroxychloroquine are used clinically with other drugs, substrates of P450 2D6 enzyme, attention should be given to substrate-specific metabolism by P450 2D6 alleles present in individuals taking the drugs.
Topics: Animals; COVID-19; Chloroquine; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Hydroxychloroquine; Membrane Transport Proteins; Pharmaceutical Preparations; COVID-19 Drug Treatment
PubMed: 33292107
DOI: 10.2174/1389200221999201208211537 -
Journal of General Internal Medicine Nov 2020There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.
OBJECTIVE
We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.
METHODS
Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.
RESULTS
We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.
AUTHORS' CONCLUSION
The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.
Topics: Bias; Chloroquine; Humans; Hydroxychloroquine; Research Design; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32885373
DOI: 10.1007/s11606-020-06146-w