Conv. Plasma
Nigella Sativa

All HCQ studies
Meta analysis
study COVID-19 treatment researchHCQHCQ (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Tolerability and pharmacokinetic evaluation of inhaled dry powder hydroxychloroquine in healthy volunteers

Aug 2022  
  Source   PDF   All Studies   Meta AnalysisMeta
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Tolerability and pharmacokinetic evaluation of an inhaled dry powder formulation of HCQ. Inhaled HCQ was generally well-tolerated, with only minor adverse effects. Pulmonary function tests found no significant drop in FEV1 after inhalation compared to baseline. ECGs showed no clinically significant QTc prolongation after inhaled HCQ doses up to 20mg. Serum HCQ levels remained very low (<10 μg/L) at all doses, indicating low systemic exposure. Single doses of inhaled dry powder HCQ up to 20mg were found to be safe and well-tolerated in healthy volunteers. The very low serum levels suggest effective lung delivery with minimal systemic exposure. The results support further clinical studies of inhaled HCQ for COVID-19 treatment.
de Reus et al., 5 Aug 2022, Netherlands, peer-reviewed, 9 authors, study period 29 September, 2020 - 16 October, 2020, trial NCT04497519 (history). Contact:
This PaperHCQAll
Tolerability and pharmacokinetic evaluation of inhaled dry powder hydroxychloroquine in healthy volunteers
Y A De Reus, P Hagedoorn, M G G Sturkenboom, F Grasmeijer, M S Bolhuis, I Sibum, H A M Kerstjens, H W Frijlink, O W Akkerman
PLOS ONE, doi:10.1371/journal.pone.0272034
Rationale Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects. Objectives To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler. Methods Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation. Results and discussion Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV 1 post inhalation. The serum HCQ concentration remained below 10 μg/L in all samples.
Supporting information S1 Checklist. CONSORT checklist. (DOC) Author Contributions
Armstrong, Gluck, Crapo, Jones, Hughes, Lung tissue volume estimated by simultaneous radiographic and helium dilution methods, Thorax, doi:10.1136/thx.37.9.676
Arshad, Kilgore, Chaudhry, Jacobsen, Wang et al., Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19, Int J Infect Dis, doi:10.1016/j.ijid.2020.06.099
Brun, De Boer, Mannes, De Fraiture, Brimicombe et al., Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2. Inhalation of a novel colistin dry powder formulation: a feasibility study in healthy volunteers and patients, Eur J Pharm Biopharm, doi:10.1016/s0939-6411%2802%2900044-9
Chen, Efficacy of hydroxychloroquine and azithromycin as a treatment of COVID-19: results of a randomized clinical trial
Cortegiani, Ingoglia, Ippolito, Giarratano, Einav, A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19, J Crit Care, doi:10.1016/j.jcrc.2020.03.005
Costedoat-Chalumeau, Dunogue, Morel, Guern, Guettrot-Imbert, Hydroxychloroquine: a multifaceted treatment in lupus, Presse Med, doi:10.1016/j.lpm.2014.03.007
Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105938
Gao, Tian, Yang, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends, doi:10.5582/bst.2020.01047
Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105949
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2012410
Geller, Konstan, Smith, Noonberg, Conrad, Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety, Pediatr Pulmonol, doi:10.1002/ppul.20594
Gies, Bekaddour, Dieudonne, Guffroy, Frenger et al., Beyond Anti-viral Effects of Chloroquine/Hydroxychloroquine, Front Immunol, doi:10.3389/fimmu.2020.01409
Graham, Steenbruggen, Miller, Barjaktarevic, Cooper et al., Standardization of Spirometry 2019 Update, An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med, doi:10.1164/rccm.201908-1590ST
Grasmeijer, Kerstjens, Frijlink, Van Der Vaart, Vonk, Colistin dry powder inhalation with the Twincer: An effective and more patient friendly alternative to nebulization, PLoS One, doi:10.1371/journal.pone.0239658
Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2118542
Harris, Taylor, Minor, Elliott, Fernandez et al., The REDCap consortium: Building an international community of software platform partners, J Biomed Inform, doi:10.1016/j.jbi.2019.103208
Harris, Taylor, Thielke, Payne, Gonzalez et al., Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support, J Biomed Inform, doi:10.1016/j.jbi.2008.08.010
Harrison, Mccarthy, Fleming, Hickey, Shortt et al., Inhaled versus nebulised tobramycin: a real world comparison in adult cystic fibrosis (CF), J Cyst Fibros, doi:10.1016/j.jcf.2014.04.004
Hoppentocht, Akkerman, Hagedoorn, Alffenaar, Van Der Werf et al., Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin Free Base in Non-Cystic Fibrosis Bronchiectasis Patients, PLoS One, doi:10.1371/journal.pone.0149768
Hoppentocht, Akkerman, Hagedoorn, Frijlink, De Boer, The Cyclops for pulmonary delivery of aminoglycosides; a new member of the Twincer family, Eur J Pharm Biopharm, doi:10.1016/j.ejpb.2015.01.012
Horby, Mafham, Linsell, Bell, Staplin et al., Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2022926
Kavanagh, Healy, Dayton, Robinson, Reilly et al., Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19, Med Hypotheses, doi:10.1016/j.mehy.2020.110110
Klimke, Hefner, Will, Voss, Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection, Med Hypotheses, doi:10.1016/j.mehy.2020.109783
Kuba, Imai, Rao, Gao, Guo et al., A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury, Nat Med, doi:10.1038/nm1267
Kuznik, Bencina, Svajger, Jeras, Rozman et al., Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines, J Immunol, doi:10.4049/jimmunol.1000702
Lammers, Brohet, Theunissen, Koster, Rood et al., Early Hydroxychloroquine but not Chloroquine use reduces ICU admission in COVID-19 patients, Int J Infect Dis
Ledford, How does COVID-19 kill? Uncertainty is hampering doctors' ability to choose treatments, Nature, doi:10.1038/d41586-020-01056-7
Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov, doi:10.1038/s41421-020-0156-0
Mahe ´vas, No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: Results of a study using routinely collected data to emulate a target trial, MedRxiv
Mdel, Aguilar-Fernandez, Cabrera-Roca, Idiopathic pulmonary haemosiderosis in childhood: a good response to systemic steroids
Mingo, Simmons, Shoemaker, Nelson, Schornberg et al., Ebola virus and severe acute respiratory syndrome coronavirus display late cell entry kinetics: evidence that transport to NPC1+ endolysosomes is a rate-defining step, J Virol, doi:10.1128/JVI.03398-14
Mulay, Konda, Garcia, Yao, Beil et al., SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery, bioRxiv, doi:10.1101/2020.06.29.174623
Nicol, Joshi, Rizk, Sabato, Savic et al., Pharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID-19 Infection, Clin Pharmacol Ther, doi:10.1002/cpt.1993
Pahan, Pahan, Smooth or Risky Revisit of an Old Malaria Drug for COVID-19?, J Neuroimmune Pharmacol, doi:10.1007/s11481-020-09923-w
Pauli, Joshi, Vasavada, Brackett, Towa, Evaluation of an Immediate-Release Formulation of Hydroxychloroquine Sulfate With an Interwoven Pediatric Taste-Masking System, J Pharm Sci, doi:10.1016/j.xphs.2019.12.014
Rynes, Hydroxychloroquine treatment of rheumatoid arthritis, Am J Med, doi:10.1016/0002-9343%2888%2990357-9
Schrezenmeier, Dorner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nat Rev Rheumatol, doi:10.1038/s41584-020-0372-x
Stower, Virological assessment of SARS-CoV-2, Nat Med, doi:10.1038/s41591-020-0848-x
Subbarao, Mcauliffe, Vogel, Fahle, Fischer et al., Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice, J Virol, doi:10.1128/jvi.78.7.3572-3577.2004
Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ, doi:10.1136/bmj.m1849
Uttley, Harnan, Cantrell, Taylor, Walshaw et al., Systematic review of the dry powder inhalers colistimethate sodium and tobramycin in cystic fibrosis, Eur Respir Rev, doi:10.1183/09059180.00001513
Westerman, Boer, Brun, Touw, Roldaan et al., Dry powder inhalation of colistin in cystic fibrosis patients: a single dose pilot study, J Cyst Fibros, doi:10.1016/j.jcf.2006.10.010
White, Watson, Hoglund, Chan, Cheah et al., COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology, PLoS Med, doi:10.1371/journal.pmed.1003252
Who, None
Yao, Ye, Zhang, Cui, Huang et al., 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
Zhou, Dai, Tong, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression, J Antimicrob Chemother, doi:10.1093/jac/dkaa114
Zhou, Dcosta, Landau, Tada, Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies, Viruses, doi:10.3390/v14061334
Zhu, Zhang, Li, Yang, Song, A Novel Coronavirus from Patients with Pneumonia in China, N Engl J Med, doi:10.1056/NEJMoa2001017
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop