In the coronavirus discussion thread within the Vitamins and Minerals 101 Premium group, one of the members asked me to look into the possibility that the anti-parasitic drug, ivermectin, could treat COVID-19.
Please note that I have a PhD in Nutritional Sciences, I am not a medical doctor, and this is not medical advice.
That ivermectin might be helpful was suggested by a study done in vitro, meaning in a lab dish. This study examined the ability of ivermectin to reduce the replication of SARS-CoV-2, the coronavirus that causes COVID-19, in isolated cells. They found that 5 micromoles per liter (uM, a measure of the number of molecules per liter) of ivermectin caused a 5000-fold reduction in the amount of virus within 48 hours, effectively completely clearing it. The concentration that eliminated half the viral RNA, known as the IC50, was between 2.2 and 2.5 uM. The minimal concentration required to have any antiviral activity at all was somewhere between 1 and 2 uM.
A new preprint* released today casts serious doubt that this in vitro study has any relevance at all.
These authors collected all the literature on ivermectin dosing that reported the blood concentrations reached with the drug.
The established doses of the drug used for various parasitic infections range from 150 to 400 micrograms per kilogram bodyweight (ug/kg), usually administered once per year, and there are also reports of the blood concentrations reached by excessive doses up to 2000 ug/kg.
The highest blood concentration reported in the literature for this drug is 283.2 nanomoles per liter (nM), from the unnecessarily high dose of 2000 ug/kg. One nanomole is a thousandth of a micromole, so this is equivalent to 0.28 uM. This is 17 times lower than the concentration required to eliminate the virus over 48 hours, 8 times lower than the concentration required to achieve 50% reduction in the virus, and somewhere between 3.5 and 7 times lower than the concentration to have any antiviral activity at all.
It took 48 hours of sustaining these concentrations to produce the antiviral effects reported in isolated cells in the first paper. But the half-life of the drug at the highest dose tested was 4.2 hours. That means the drug would be gone after one day, and the peak concentration would only be sustained for a short period of time, not for 48 hours.
The ivermectin doses are used once a year, and sometimes once every three months. To sustain a concentration in the blood over time, the drug has to be dosed repeatedly. For example, dosing the drug once every half life will sustain a concentration roughly double of the peak concentration reached after a single dose. 2000 ug/kg (120 mg for the average person) every 4 hours would be expected to eventually produce a steady concentration of about 0.58 uM, still well under the concentration needed to be effective. Sustaining the concentrations required to eliminate the virus for 48 hours would likely require 5-10 times this.
Such doses are probably wildly unsafe. The drug is never used at anywhere near those doses therapeutically, and the literature includes an overdose at 200 milligrams, which is about 67% greater than the highest dose for which we know the peak blood concentrations. This was a 46-year-old man who developed drowsiness, unconsciousness, weakness, inability to control his movements, and visual changes. Achieving antiviral activity against SARS-CoV-2 would probably have required him to take 3-6 times this dose every four hours for two days, at which point the toxicity could have been far worse and perhaps lethal.
At the present time, ivermectin should not be considered a safe way to prevent or treat COVID-19.
Stay safe,
Chris
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Disclaimer
I am not a medical doctor and this is not medical advice. I have a PhD in Nutritional Sciences and my expertise is in conducting and interpreting research related to my field. Please consult your physician before doing anything for prevention or treatment of COVID-19, and please seek the help of a physician immediately if you believe you may have COVID-19.
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*Footnotes
* The term “preprint” is often used in these updates. Preprints are studies destined for peer-reviewed journals that have yet to be peer-reviewed. Because COVID-19 is such a rapidly evolving disease and peer-review takes so long, most of the information circulating about the disease comes from preprints.