Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19
Oisín Kavanagh, Anne Marie Healy, Francis Dayton, Shane Robinson, Niall J O'reilly, Brian Mahoney, Aisling Arthur, Gavin Walker, John P Farragher
Medical Hypotheses, doi:10.1016/j.mehy.2020.110110
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
PeakProsperity for simulating their first discussions on this topic.
Declaration of Competing Interest The authors declare that they have no competing financial interest. The HCQ formulation was developed and IP filed by APT Corporation. The clinical and regulatory work was done by Aradigm under contract to, and paid for by APT. While both corporations no longer exist, the rights to the data have since been licensed to Pulmoquine and development is progressing for COVID-19. Appropriate intellectual property has been filed.
Authorship statement JF conceptualised this project. OK and AMH drafted the manuscript and OK preformed the analysis of the ClinicalTrials.gov data. FD provided the phase I and II clinical data and described the formulation. Discussions with SR, JF, NO'R and BM helped develop the idea. GW and AMH acquired funding to support the project. AA was responsible for logistical arrangements. All authors reviewed and agreed to the final manuscript.
Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.mehy.2020.110110.
References
Arnold, Buckner, Hydroxychloroquine for treatment of SARS-CoV-2 infection? Improving our confidence in a model-based approach to dose selection, Clin Transl Sci,
doi:10.1111/cts.12797Belitz, Wieser, Food Reviews International Bitter compounds: Occurrence and structure-activity relationships BITTER COMPOUNDS: OCCURRENCE AND STRUCTURE-ACTIVITY RELATIONSHIPS, Food Rev Int
Bonow, Hernandez, Turakhia, Hydroxychloroquine, Coronavirus Disease 2019, and QT Prolongation, JAMA Cardiol
Dayton, Communication, Clinical Study Report: A two-part, randomised, double-blind, placebo-controlled, ascending-dose study to evaluate the safety, tolerance and pharmacokinetics of orally inhaled hydroxychloroquine sulfate via the AERx System in healthy adult volunteers, Sponsor Protocol No
Dayton, Communication, Clinical study Report: A randomised, doubleblind, placebo-controlled, multiple-dose study to evaluate the safety, tolerance and efficacy of orally inhaled hydroxychloroquine sulfate (HCQ) via the AERx® System in asthmatic subjects, Sponsor Protocol No
Dayton, None
Dayton, Owen, Cipolla, Development of an inhaled hydroxychloroquine sulfate product using the AERx ® system to treat asthma, Respir Drug Deliv
Dörner, Therapy: hydroxychloroquine in SLE: old drug, new perspectives, Nat Rev Rheumatol
Garcia-Cremades, Solans, Hughes, Optimizing hydroxychloroquine dosing for patients with COVID-19: An integrative modeling approach for effective drug repurposing, Clin Pharmacol Ther
Gorbalenya, Baker, Baric, The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat Microbiol
Hoffmann, Kleine-Weber, Krueger, Mueller, Drosten et al., The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells, Internet
Klimke, Hefner, Will, Voss, Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection, Med Hypotheses
Morice, Kardos, Comprehensive evidence-based review on European antitussives, BMJ Open Respir Res
Morris, Tisi, Tan, Worthington, Development and palatability assessment of norvir® (Ritonavir) 100 mg powder for pediatric population, Int J Mol Sci
Pauli, Joshi, Vasavada, Brackett, Towa, Evaluation of an immediaterelease formulation of hydroxychloroquine sulfate with an interwoven pediatric taste-masking system, J Pharm Sci
Rabkin, Aging effects on QT interval: implications for cardiac safety of antipsychotic drugs, J Geriatr Cardiol
Rabkin, Cheng, Thompson, Detailed analysis of the impact of age on the QT interval, J Geriatr Cardiol
Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): a review, JAMA -J Am Med Assoc
Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases?, Lancet Infect Dis
Savarino, Trani, Donatelli, Cauda, Cassone, New insights into the antiviral effects of chloroquine, Lancet Infect Dis
Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Weinstein, Anderson, The aging kidney: physiological changes, Adv Chronic Kidney Dis
Wise, Breslin, Dalton, Effect of taste sensation on cough reflex sensitivity, Lung
Wise, Breslin, Dalton, Sweet taste and menthol increase cough reflex thresholds, Pulm Pharmacol Ther
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis
