Ivermectin and COVID-19

[seaexplorer]

Hello all,

I want to share my personal experience with the use of Ivermectin for treatment of COVID-19.

Three weeks ago I never even heard of this drug but today I consider it one of the most to be thankful for.

There weeks ago I got a call from my son telling me he and his girlfriend have tested positive for COVID-19. It came from the brother of the girlfriend and her parents.

When I got the news I felt my stomach fall to the ground and a surge of adrenaline hit from the shock of hearing that my son now has this frightening virus. He assured me he feels ok and will fight it off. He’s a very healthy young man. Very passionate with body weight exercises and just super strong and health. I’d even say he’s much stronger than bulked up bodybuilders because he does one arm pull ups and handstand push-ups, but that’s beside the point. He’s strong and healthy. And young. 25. He’ll get through I told myself.

The next day I get a call from the gf. My son took a sudden turn for the worse and they just got home from the ER. He couldn’t walk more than 5 ft and had to be carried. His strength was basically zero. The ER sent him home because he was breathing fine. Standard operating procedure.

The next day he’s even worse. I’m now officially scared. He’s instructed to stay home unless he’s having problems breathing. His girlfriend, who also has the virus, is a wreck. I felt helpless but had to do something. Anything.

i managed to get a phone appt with my Dr. I told him what’s going on and if he knew of anything that can be done. He told me he has been treating patients using Ivermectin and having 100% success rate if it’s started early. WTH is Ivermectin can you write me a prescription, I asked. He explained it isn’t approved and that it’s for treating head lice and parasites. He heard of it from his son who is also a Dr.

My Dr. then explained that since I live across the border in Mexico, I can just go to any farmacia and buy it. It’s cheap. The protocol he was using is 6mg a day for 8 days. He said to get it and overnight it to my son. The second I get of the phone, I run to the nearest farmacia. I actually had to go to a few because word already got out here in Mexico. I finally managed to buy enough for my son and four others, and I got some for myself and wife for insurance. I then overnight to my son who lives 800 miles away.

Here is the chronological result:

Day 1
My son was so weak and lethargic, he couldn’t eat or really even take a pill. His gf smashed the tablet and mixed it in juice and froze it making it an Ivermectin popsicle that he can suck on.

Day 2
My son is less lethargic and is able to drink from a glass. He takes his dose and his gf makes him drink lots of Pedialyte all day due to not being able to eat or drink the past few days.

Day 3
My son feels alert and he’s starting to get his sense of smell back. He’s able to talk on the phone. His appetite is back and he’s eating vigorousl.

Day 4
He feels almost normal. Just a little weak still be pretty good

Day 5
He feels normal

Days 6,7,8
He continues to regain strength. On day 8 he resumes working out. He’s bummed he lost some strength and can ”only” do 10 one arm pushups.

Its now been a couple weeks. My son is back to running and working out and basically being 100% recovered.

Oh, and the other four people that also got the medicine? They weren’t as bad as my son, but all of them started to feel better after 2-3 days and all are 100% cured.

I witnessed my son go from a lethargic near vegetable to being able to return to working out in little over a week. This is incredible. You have no idea the relief I feel. Thank god for Ivermectin. A drug I didn’t know exist just a couple weeks ago.

Why isn’t this being used more? Well, the many double blind, peer reviewed studies have to happen to make sure it’s effective. And safe. That’s the right way to go about it but when it was my son and I saw how bad he got, screw the double blind random peer review studies. He had nothing to lose. I’m glad my Dr told me of this drug and the results I saw were amazing.

I don’t know why this isn’t being given more attention. Anyway, this is my experience with Ivermectin and I wanted to share them.

 

[fifty]

Thanks for the info.

 

[Cataceous]

Those of us with equine connections are quite familiar with ivermectin as an animal dewormer. Pretty weird that may work against a virus.

 

[DragonBits]

@seaexplorer

I would say the reason this hasn't been more widely disseminated and given more attention is the study about covid-19 was done in vitro with doses 35 times higher than the approved dose in humans.

They said they have increased dosage 10 times higher, and have had some limited success, but are looking at inhaled ivermectin.

So it looks promising, but a lot of tweaking likely needs to be done, if possible.
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The approved dose of ivermectin alone not useful in treating COVID-19


A new paper published on the preprint server medRxiv in April 2020 shows that the use of the already approved drug ivermectin in clinical trials to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not feasible. This contradicts earlier reports of its ability to suppress the virus in vitro.

An earlier research article published in the journal Antiviral Research claimed that ivermectin in vitro had an inhibitory action on the novel coronavirus, reducing the load of viral RNA by 5,000 times at 48 hours. The ivermectin dose used in this study was 5 μM.

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Plasma concentration of ivermectin

The in vitro study used ivermectin a0t a concentration that inhibits 50% of proliferating viruses (IC50). This concentration of 2 μM is 35 times higher than the maximum plasma concentration achieved in blood on oral administration of ivermectin at the approved dose of approximately 200 μg/kg. And this refers to the total plasma concentration.

Ivermectin is bound extensively by plasma protein, to the tune of 93%, which means that the maximum concentration of unbound ivermectin in the plasma is several orders of magnitude less.

When oral ivermectin is administered in humans, it reaches the lungs in unbound form, and the final concentration also depends on the presence of specific transport proteins that can keep the drug in the lung tissue, as well as how rapidly it binds to and crosses the fatty cell membrane of the cell.

Unrealistic dosing

The actual concentration in the human lung cannot be measured. In cattle experiments, a single dose was shown to produce lung levels almost three times higher than the total plasma level. Despite this, lung ivermectin concentrations are “unlikely to reach the IC50 after oral administration of the approved dose in humans,” say the researchers.

Ivermectin has a wider therapeutic margin, allowing some increase in the dose if warranted, without unduly pushing up the risk of toxicity. This has led to the evaluation of higher than usual doses of ivermectin in a phase 3 trial to assess the safety. Another phase I trial looked at doses, 10-fold the approved dose.

The results showed the drug was tolerated with the ten-fold dosing regime as well as at 60 mg three times a week.

How was the study done?

The current study was aimed at analyzing the human dose necessary to achieve the experimental IC50 in the lungs. This is crucial to planning a clinical trial.

The researchers used a population model to study the pharmacokinetics of the drug. This included the transit absorption, drug elimination, and weight of the patient. The model was based on healthy participants who took 12 mg ivermectin orally after food.

A hundred simulations of total and bound ivermectin were performed to track the total plasma concentration-time profile. Different doses were used, such as the approved dose of 200 μg/kg, 120 mg in a single weekly dose, and 60 mg three times a week (at 72-hour intervals, in healthy subjects).

These additional simulations were carried out because of the observation that after a subcutaneous dose, ivermectin levels remained stable in cattle lungs for eight days. They then declined slowly over 30 days.

The concentration-time graph for unbound plasma ivermectin was also predicted from the data. Maximum total plasma concentrations were derived.

What did the results show?

The researchers found that the plasma concentrations, whether of total, bound, or unbound ivermectin did not reach the IC50 even with a tenfold rise in the dosage or after repeated dosing. The lung concentration in cattle is 2.7 times higher than in plasma, but even so, lung concentrations fall short of the IC50 of 2 μM.

To reach this level, ivermectin would need to accumulate in the lungs more than 25 times the calculated rate at the approved weekly dose. For the weekly 120 mg dose, it would need to build up over 2.5 times. With the 72-hourly dosing of 60 mg, it would have to rise to 5 times the observed level.

The estimated accumulation ratio in the lung tissue is 2.20, which results in lung concentrations reaching only a tenth of the IC50 at the approved dose given three times a week. Even with daily dosing at approved doses, it rises to only a fourth of the IC50

What are the implications of the study?

The current approach to finding a viable therapy for the SARS-CoV-2 is to repurpose existing drugs. All over the world, ivermectin came into widespread use of off-label in response to the news of the in vitro success against the virus.

At a dose of 150 μg/kg, observation of 52 patients on mechanical ventilation appeared to show clinical benefit with the drug in contrast to over 1,900 patients on conventional treatment. Though these results need to be analyzed to rule out confounding factors and biases, on the surface, they would seem to suggest that very low lung concentrations of ivermectin are able to inhibit the virus.

In other words, even when the ivermectin concentration is not anywhere near the IC50, it appears to have antiviral activity. This could suggest that the lung distribution or accumulation of this drug is far greater in humans than in cattle.

In contrast, the concentrations of ivermectin reported inhibiting the coronavirus in vitro were markedly higher than those achieved in human lung or plasma with the approved doses of ivermectin. As a result, say the researchers, “the likelihood of a successful clinical trial using the approved dose of ivermectin is low.”

This should be a warning to conduct in vitro studies of repurposed drugs at concentrations that are safe and tolerable in humans.

Future recommendations

The researchers advise a dose-response study using a control group, as well as testing the possibility of inhaled ivermectin and combination therapy.

The dose-response study should begin with the addition of potentiating compounds to reduce the threshold of viral inhibition to the tune of 0.1 μM rather than the 5 μM of the original experiment. Close monitoring is required since these dosage levels and protocols have not been widely studied.

Inhaled ivermectin would allow for higher dosage and increased local lung concentrations without additional systemic exposure. However, preclinical studies of its safety and tolerability are required.

The study sums up: “Ivermectin is unlikely to reach the IC50 in lungs after oral administration of the approved dose or doses 10x higher than the approved doses as a single dose. The approved dose of ivermectin alone has a low probability of success in the treatment of COVID-19.”

Important Notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Correction
It has come to our attention that the original title of this article, "Ivermectin alone not useful in treating COVID-19" was inadvertently misleading. The title has been corrected to better reflect the research paper's title, "The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19".

 

[seaexplorer]

The dose my son and his girlfriend (and a couple others) took was just a 6mg tablet a day for 8 days. All I know is my son made a dramatic improvement very fast and the others all fully recovered within a few days. I was so scared there for a few days seeing him go downhill so fast.

There’s more reports emerging of its successful use. Here’s a news clip from a Dr in Florida using it to treat his patients: News clip

I hope it turns out to help the majority. I see some studies have started. Johns Hopkins has a study scheduled to have some results next month.

 

[DragonBits]

The dose my son and his girlfriend (and a couple others) took was just a 6mg tablet a day for 8 days. All I know is my son made a dramatic improvement very fast and the others all fully recovered within a few days. I was so scared there for a few days seeing him go downhill so fast.

There’s more reports emerging of its successful use. Here’s a news clip from a Dr in Florida using it to treat his patients: News clip

I hope it turns out to help the majority. I see some studies have started. Johns Hopkins has a study scheduled to have some results next month.

First, glad your son and others recovered.

From what I have read, it's very plausible that this drug helped.