A standard dose of ivermectin was given to a small number (13) patients late in the disease without obvious benefit.
The discussion contains this (and some references) which seems important:
In the last years, high doses of IVM have been evaluated for the treatment of soil-transmitted helminths [7–10] and as a new vector control tool to reduce malaria transmission in malaria endemic areas [11]. Recent studies have evaluated doses up to 800 μg/kg, given in single dose or three consecutive days [9, 11, 12], showing a good safety profile both in adult and paediatric populations. Subjective ocular problems such as transitory blurred vision appeared, but no severe adverse events were reported with these high doses [11, 12].
These findings, including a recent meta-analysis of the safety of high doses of ivermectin [7], add evidence of the safety of IVM at doses up to 800 μg/kg, which has a safety profile comparable to lower doses of 200 or 400 μg/kg. Moreover, the results of the meta-analysis do not suggest an increased number of adverse events with increasing doses of IVM. The maximum doses of IVM given to study participants have been published in a study with a limited number of participants, in which doses up to 2000 μg/kg were received by 12 participants, showing a similar rate of adverse events than those receiving placebo [13]. However, the antiviral efficacy of these high doses of IVM should be still evaluated in clinical studies, since some authors have recently suggested that in vitro inhibitory concentrations of 5umol/L (those needed for a total eradication of SARS-CoV-2 in in vitro studies) would not be attainable even using high doses of ivermectin (2000ug/kg) [4, 14].
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Several References
4.Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020:104787.
7.Navarro M, Camprubí D, Requena-Méndez A, et al. Safety of high-dose ivermectin: a systematic review and meta-analysis. J Antimicrob Chemother. 2020;75(4):827–834.
8.Muñoz J, Ballester RM, Antonijoan RM, et al. Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers. PLoS Negl Trop Dis. 2018;12(1):e0006020. pmid:29346388
9.Wimmersberger D, Coulibaly JT, Schulz JD, et al. Efficacy and safety of ivermectin against Trichuris trichiura in preschool-aged and school-aged children: a randomized controlled dose-finding trial. Clin Infect Dis 2018; 67: 1247–55.
10.Buonfrate D, Salas-Coronas J, Muñoz J, et al. Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial. Lancet Infect Dis. 2019;19(11):1181–1190.
11.Smit MR, Ochomo EO, Aljayyoussi G, et al. Human Direct Skin Feeding Versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial). Clin Infect Dis. 2019;69(7):1112–1119.
14.Momekov G, Momekova D.
Ivermectin as a potential COVID-19 treatment from a pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens. Biotechnology & Biotechnological Equipment, 34:1, 469–474.
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This last reference by Momekov gives the opinion that the virocidal effects that
Caly demonstrated of Ivermectin on SC2 infected tissue culture cells will not be seen in humans as it is just not possible to get the drug concentrations in humans using "known dosing regimens."
So this is a summary of the "ivermectin is not effective" literature.
I don't see discussion of the differential concentration of ivermectin by different tissues (known to be concentrated in lung tissue in cattle, for example) or the multiple studies showing clinical evidence of benefit.
