Conv. Plasma
Nigella Sativa

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

All Studies   Meta Analysis   Recent:  

Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats

Chaccour et al., Scientific Reports, doi:10.1038/s41598-020-74084-y
Oct 2020  
  Source   PDF   All Studies   Meta AnalysisMeta
Study showing that nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats. Authors note that additional experiments are required to assess the safety of this formulation in larger animals.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin is an inhibitor of importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), a SARS-CoV-2 3CLpro inhibitor Mody, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model of severe infection/inflammation that shares key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacterium which plays a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
6 studies investigate novel formulations of ivermectin for improved efficacy Albariqi, Albariqi (B), Chaccour, Errecalde, Mansour, Saha (B)
Chaccour et al., 13 Oct 2020, peer-reviewed, 8 authors.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperIvermectinAll
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Carlos Chaccour, Gloria Abizanda, Ángel Irigoyen-Barrio, Aina Casellas, Azucena Aldaz, Fernando Martínez-Galán, Felix Hammann, Ana Gloria Gil
Scientific Reports, doi:10.1038/s41598-020-74084-y
Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean C max 86.2 ng/ml vs. 26.2 ng/ ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals. As of August 19, 2020, there have been more than 22 million COVID-19 cases causing over 785,000 deaths worldwide. In the absence of a vaccine, numerous efforts are ongoing to develop drug-based strategies to prevent, treat or reduce the transmission of the virus. Data on several drug regimens suggest lack of efficacy for lopinavirritonavir 1 , hydroxychloroquine as prophylaxis 2 or even harmfulness such as high-dose hydroxychloroquine for prophylaxis 3 while remdesivir 4 and dexamethasone 5 seem to improve patients' outcome. Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses including Dengue 6 , Zika 7 and other viruses 8 . The effect on flaviviruses could be explained by a reduction of the viral penetration into the nucleus via an effect on the host´s importin alpha/beta1 9 , inhibition of the viral helicase 8 or yet to be described mechanisms. Caly et al. showed a significant reduction of SARS-CoV-2 replication after incubating Vero cells, a cell line derived from African Green Monkey kidney epithelial cells, for 48 h with ivermectin concentrations not readily attainable in vivo 10 .
Author contributions Competing interests The authors declare no competing interests.
Baraka, Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus, Eur. J. Clin. Pharmacol
Barrows, A screen of FDA-approved drugs for inhibitors of Zika virus infection, Cell Host Microbe, doi:10.1016/j.chom.2016.07.004
Beigel, Remdesivir for the treatment of covid-19-preliminary report, N. Engl. J. Med, doi:10.1056/NEJMoa2007764
Borba, Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial, JAMA Netw. Open, doi:10.1001/jamanetworkopen.2020.8857
Boulware, A randomized trial of hydroxychloroquine as postexposure prophylaxis for covid-19, N. Engl. J. Med, doi:10.1056/NEJMoa2016638
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir. Res, doi:10.1016/j.antiviral.2020.104787
Chaccour, Del Pozo, Case 23-2012: a man with abdominal pain and weight loss, N. Engl. J. Med, doi:10.1056/NEJMc1210168#SA2
Chaccour, Hammann, Ramon-Garcia, Rabinovich, Ivermectin and novel coronavirus disease (COVID-19): keeping rigor in times of urgency, Am. J. Trop. Med. Hyg, doi:10.4269/ajtmh.20-0271
Changeux, Amoura, Rey, Miyara, A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications, C. R. Biol, doi:10.5802/crbiol.8
Ci, Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogenactivated protein kinase activation pathway, Fundam. Clin. Pharmacol, doi:10.1111/j.1472-8206.2009.00684.x
El-Khatib, Lehnert, Lung density changes observed in vivo in rat lungs after irradiation: variations among and within individual lungs, Int. J. Radiat. Oncol. Biol. Phys, doi:10.1016/0360-3016(89)90494-x
Eraslan, Comparative pharmacokinetics of some injectable preparations containing ivermectin in dogs, Food Chem. Toxicol, doi:10.1016/j.fct.2010.05.043
Ferrell, Koong, Influence of plane of nutrition on body composition, organ size and energy utilization of Sprague-Dawley rats, J. Nutr, doi:10.1093/jn/116.12.2525
Gil, Silvan, Illera, Illera, The effects of anesthesia on the clinical chemistry of New Zealand White rabbits, Contemp. Top. Lab. Anim. Sci
Homeida, The lack of influence of food and local alcoholic brew on the blood level of Mectizan((R)) (ivermectin), Acta Trop, doi:10.1016/j.actatropica.2013.03.019
Horby, Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report, doi:10.1101/2020.06.22.20137273
Krause, Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor, Mol. Pharmacol, doi:10.1124/mol.53.2.283
Lei, Study on the subacute inhalation toxicity of Ivermectin TC in rats, Chin. J. Comp. Med
Lifschitz, Comparative distribution of ivermectin and doramectin to parasite location tissues in cattle, Vet. Parasitol, doi:10.1016/s0304-4017(99)00175-2
Maclean, Valentine, Jatlow, Sofuoglu, Inhalation of alcohol vapor: measurement and implications, Alcohol Clin. Exp. Res, doi:10.1111/acer.13291
Mastrangelo, Ivermectin a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, J. Antimicrob. Chemother, doi:10.1093/jac/dks147
Mathiasen, Moser, The Irwin test and functional observational battery (FOB) for assessing the effects of compounds on behavior, physiology, and safety pharmacology in rodents, Curr. Protoc. Pharmacol, doi:10.1002/cpph.43
Mcivor, Berger, Pack, Rachlis, Chan, An effectiveness community-based clinical trial of Respirgard II and Fisoneb nebulizers for Pneumocystis carinii prophylaxis with aerosol pentamidine in HIV-infected individuals. Toronto Aerosol Pentamidine Study (TAPS) Group, Chest, doi:10.1378/chest.110.1.141
Melotti, The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer, EMBO Mol. Med, doi:10.15252/emmm.201404084
Montgomery, Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome, Lancet, doi:10.1016/s0140-6736(87)91794-6
Nishiyama, Yokoyama, Hanaoka, Liver function after sevoflurane or isoflurane anaesthesia in neurosurgical patients, Can. J. Anaesth, doi:10.1007/BF03012146
Ouedraogo, Efficacy and safety of the mosquitocidal drug ivermectin to prevent malaria transmission after treatment: a double-blind, randomized, clinical trial, Clin. Infect. Dis, doi:10.1093/cid/ciu797
Pacanowski, Subcutaneous ivermectin as a safe salvage therapy in Strongyloides stercoralis hyperinfection syndrome: a case report, Am. J. Trop. Med. Hyg
Papadatos, Nontraumatic rhabdomyolysis with short-term alcohol intoxication-a case report, Clin. Case Rep, doi:10.1002/ccr3.326
Russo, COVID-19 and smoking: is nicotine the hidden link?, Eur. Respir. J, doi:10.1183/13993003.01116-2020
Salluh, Successful use of parenteral ivermectin in an immunosuppressed patient with disseminated strongyloidiasis and septic shock, Intensive Care Med
Schwartz, Hams, Fallon, Helminth modulation of lung inflammation, Trends Parasitol, doi:10.1016/
Sutherland, Leathwick, Anthelmintic resistance in nematode parasites of cattle: a global issue?, Trends Parasitol, doi:10.1016/
Vanapalli, Orange juice decreases the oral bioavailability of ivermectin in healthy volunteers, Clin. Pharmacol. Ther, doi:10.1016/S0009-9236(03)90702-8
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin alpha/betamediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J, doi:10.1042/BJ20120150
Wiberg, Trenholm, Coldwell, Increased ethanol toxicity in old rats: changes in LD50, in vivo and in vitro metabolism, and liver alcohol dehydrogenase activity, Toxicol. Appl. Pharmacol, doi:10.1016/0041-008x(70)90077-3
Yang, Tekwani, Martin, In COVID-19, adding lopinavir-ritonavir to usual care did not shorten time to clinical improvement, Ann. Intern. Med, doi:10.7326/ACPJ202006160-063
Yang, The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer, Antiviral Res, doi:10.1016/j.antiviral.2020.104760
Zhang, Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflamm. Res, doi:10.1007/s00011-008-8007-8
Zhang, Protective effect of abamectin on acute lung injury induced by lipopolysaccharide in mice, Fundam. Clin. Pharmacol, doi:10.1111/j.1472-8206.2010.00896.x
Please send us corrections, updates, or comments. c19early involves the extraction of over 100,000 datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, 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