Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID‐19

Pena‐Silva, Ricardo A.; Duffull, Stephen B.; Steer, Andrew C.; Jaramillo-Rincón, Sandra; Gwee, Amanda; Zhu, Xiao

doi:10.1111/bcp.14476

Cited by 45 publications

(36 citation statements)

References 10 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, a number of caveats have been pointed out regarding the dose of ivermectin necessary to reduce SARS-CoV-2 viral replication. Most of them point out the need for ivermectin at doses 200 times lower than the dose reported by Carly et al (2020) to promote a reduction in SARS-CoV-2 in vitro viral replication [ 5 , 6 ]. Our results not only corroborate that higher doses have a greater antiviral effect, but also show that supra-lethal toxic doses are unnecessary to inhibit viral replication.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, ivermectin’s antiviral effect was tested in vitro in Vero/hSLAM cells infected with SARS-CoV-2 (isolate Australia/VIC01/2020) [ 5 ].⁠ After 48 h, there was a 5000-fold reduction in viral RNA in ivermectin-treated samples as compared to controls. Although these findings highlighted the potential use of ivermectin as an antiviral drug in the fight against COVID-19, the dose used was 200 times greater than those commonly used in clinical indications [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RETRACTED: Use of ivermectin in the treatment of Covid-19: A pilot trial

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED: Use of ivermectin in the treatment of Covid-19: A pilot trial

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, the as far as IVM is concerned, by virtue of having a high plasma protein binding of 93%, its uptake by endothelial cells is limited [ 50 ]. With regard to the pulmonary distribution of IVM, while adequate literature is not available describing the accumulation of IVM in the lungs when administered to human subjects, the concentrations of IVM reaching cattle lungs after injecting the drug at a dose of 200 μg/kg was approximately 0.1 μM, which is significantly less than the 5-μM IVM concentration that was used in the Caly study to inhibit the growth of SARS-CoV-2 in vitro [ 9 , 51 , 52 ]. Considering that the conventional dose of IVM for treating strongyloidiasis is a single 200-μg/kg oral dose, there is no evidence that this dosing schedule would result in IVM reaching an antiviral concentration in the lungs [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review

Bhowmick

Dang²,

Vallish³

et al. 2021

Drug Saf

View full text Add to dashboard Cite

Introduction and Objective Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management. Methods After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design. Results Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and ‘hydroxychloroquine + azithromycin’ in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a ‘good’ methodological quality. Conclusions Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management. Systematic Review Protocol Registration Details Open Science Framework: https://osf.io/n7r2j . Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01066-y.

show abstract

“…Given that SARS-CoV-2 does not encode any neuraminidase protein, neuraminidase inhibitors such as oseltamivir, zanamivir or lamivir are not thought to be effective for treating patients with COVID-19 . However, some studies have found that drugs including arbidol (Zhu et al, 2020), fusion peptide (EK1) (Xia et al, 2019), ganciclovir (Lai et al, 2020), Abelson (Abl) kinase inhibitor (imatinib) (Bernal-Bello et al, 2020), metronidazole (Gharebaghi et al, 2020), antiprotozoal drugs (nitazoxanide and ivermectin) (Mahmoud et al, 2020;Peña-Silva et al, 2020), and 3CL(Pro) inhibitors (Rathnayake et al, 2020) are efficacious when used to prevent SARS-CoV-2 infections in vitro. However, their safety and efficacy in preventing COVID-19 in humans remains to be determined.…”

Section: Other Drugsmentioning

confidence: 99%

COVID-19: the epidemiology and treatment

Ren

2020

Br J Hosp Med

View full text Add to dashboard Cite

After initially emerging in late 2019, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to cause a global pandemic. SARS-CoV-2 is a betacoronavirus that is closely related to severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, all of which can cause severe lung injury, respiratory distress and cytokine storm. While mortality rates associated with SARS-CoV-2 are lower than those associated with severe acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus, it is more contagious and spreads more rapidly than these other viruses. This article summarises the epidemiology and potential options for treating COVID-19 to give a foundation for future studies of the diagnosis, treatment and prevention of this deadly disease.

show abstract

Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID‐19

Cited by 45 publications

References 10 publications

RETRACTED: Use of ivermectin in the treatment of Covid-19: A pilot trial

RETRACTED: Use of ivermectin in the treatment of Covid-19: A pilot trial

Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review

COVID-19: the epidemiology and treatment

Contact Info

Product

Resources

About