Pharmacokinetics of Ivermectin in Animals and Humans (US 1987) Describes accumulation of ivermectin in tissues

[-] DreadPyriteRoberts | 6 points | Dec 25 2020 03:07:19

Edit: Having now read the paper -- there is nothing in the paper supporting the theory that ivermectin is stored in the fatty tissues. That theory must come from some other study.

This paper is NOT the basis for an interesting feature of the FLCCC's I-MASK+ prophylaxis schedule:

Prophylaxis for high risk individuals 0.2 mg/kg — one dose on day 1 and day 3, then take one dose weekly for 10 weeks, followed by one dose every 2 weeks *

** This dosing may be updated as further scientific studies emerge.

Why does it make sense to cut back to every-other-week, after 10 weeks of dosing weekly? Because ivermectin accumulates in the tissues. However, this paper doesn't present anything supporting that theory.

[-] Ahambo_Abhivaadaye | 3 points | Dec 25 2020 17:35:29

Apologies for dumb, stupid question. I'm a layman. Would that accumulation causes any side-effect/toxicity or any adverse effect on other organs?

[-] TrumpLyftAlles | 1 points | Dec 26 2020 19:23:20

AFAIK, no one knows. There isn't a medical condition that is treated with continuing long-term dosing of ivermectin.

The main theory about how ivermectin fights covid19 is it blocks the imp alpha/beta1 mechanism that the virus uses to send proteins into the cell nucleus, which disable the cell's immune response. Presumably that mechanism exists because it's needed, implying that blocking it has deleterious effects. What are they? I don't know.

That said, in the Argentina prophylaxis trial, 788 health workers took 12mg ivermectin weekly for 3 months, and no serious adverse side-effects were reported. However, did that study look for possible downsides, like looking at the subjects' liver and kidney panels? Nope.

In the context of a virus that kills a lot of patients and leaves a lot of others with organ damage and months-long recuperation, it's a trade-off of risk.

[-] Impressive_Run8581 | 2 points | Dec 26 2020 23:10:44

FLCCC isn't well thought out and doesn't follow the science. AT least they updated v5 to v6 for the prophylaxis. The 'heartworm' analogy and basis was comical.

[-] DreadPyriteRoberts | 1 points | Dec 27 2020 16:12:15

doesn't follow the science.

What specifically about the FLCCC protocol do you think is wrong? Going to every other week after the 10 weekly doses?

[-] luisvel | 2 points | Dec 25 2020 17:09:40

Given it’s for prophylaxis and it seems to accumulate, wouldn’t it be much better to receive low frequent doses to ensure the concentration keep stable? Is that regimen proposed just due to its simplicity or is there something else to it? As taking frequent micro doses may be even safer, because any potential side effect will build up instead of showing up quick on the first dose which may scare some people. Is there any biologist/MD that could reply that around?

[-] Haitchpeasauce | 3 points | Dec 26 2020 01:47:38

Not a biologist or MD, feel free to disregard all below.

Marik uses loading doses with steroids as well, and with Ivermectin it makes intuitive sense when looking at the graphs. You will note an initial peak, followed by a steady decline, but the overall level is higher when a higher initial dose is used.

Therefore more frequent initial dosing overcomes the elimination rate of the liver until therapeutic amounts have accumulated in the tissues. As a highly lipophilic molecule, Ivermectin is going to be take up quickly by fats as well.

Small frequent doses may eventually achieve the right levels, but we want effective levels as soon as possible. Once achieved, a bigger weekly dose is going to be easier and cheaper to follow than daily smaller dose.

For treating active infection, it makes sense for Ivermectin to need to be more present in the plasma to be effective, so treatments that dose daily are starting to make more sense to me.

[-] my-tech-reddit-acct | 1 points | Dec 28 2020 00:33:48

Typical HCQ treatments use loading dose, too, as do HCQ prophylaxis.

[-] TrumpLyftAlles | 2 points | Dec 26 2020 19:45:51

Given it’s for prophylaxis and it seems to accumulate, wouldn’t it be much better to receive low frequent doses to ensure the concentration keep stable?

I like your reasoning and that's why I dose twice a week. The first phase of the Argentina ivermectin study had subjects dosing with ivermectin every day. They went to 12mg weekly doses for the second phase. Why? I don't recall that the study protocol (posted to the sub) says. More convenience = better compliance seems plausible.

From this study of Medicell technology and cattle comes this image which shows the plasma level of ivermectin increasing after ~85 days after dosing and peaking around 240 days. MedinCell's tech is supposed to secrete ivermectin over time, which confuses things, but the apparent implication of the chart is that ivermectin stored in the tissues is released into the blood stream long after dosing.

There are also results (posted to the sub) of a New Guinea study where 90% of villagers were scabies-free (IIRC) two years after taking ivermectin. I called this the magic of ivermectin, unaware at the time of the "it gets stored in the tissues" phenomenon.

Edit: Note the huge initial dose in the Medincell chart: 4mg/kg! That's twice the maximum dose in the Guzzy safety trial. The day 240 peak is a quarter of the initial blood levels. That huge dose could be thought of as a loading dose as /u/haitchpeasauce describes.

[-] luisvel | 2 points | Dec 26 2020 19:52:53

It makes sense to have a loading phase if you want to peak concentration faster, but at a cost of more potential stomach issues. I take creatine and when I load I always have a lateral pain I don’t get if I build up concentration.

[-] TrumpLyftAlles | 1 points | Dec 26 2020 19:56:11

I dose twice a week, no stomach problems, but I have an iron stomach and I'm unaware of having one 99% of the time.

I bought some creatine but haven't started taking it. What ramp-up dosing would you recommend?

[-] luisvel | 2 points | Dec 26 2020 20:13:22

I take it as it’s both a nootropic and a physical performance enhancer. I usually cycle 3 months on, 1 off, doing 20g daily for a week, then 5g daily for maintenance. You need to take lots of water during the loading phase if you try it.

[-] TrumpLyftAlles | 2 points | Dec 26 2020 22:30:41

I take it as it’s both a nootropic

So -- mental acuity? That's OK, I can search /r/nootropic for more information.

[-] DreadPyriteRoberts | 1 points | Dec 26 2020 20:37:55

Wow, that's a lot! No wonder it comes in massive quantities. I hazard the guess that you can't project your creatine experience to ivermectin.

Creatine is useful for muscle building, right?

A year ago I had a fall where I messed up both legs and was bedridden for two months. It's amazing how rapidly muscle tissue goes away: when I was finally able to walk (with a knee brace on one leg and a boot on the other), my legs were super-skinny and walking exhausted me. I have worked up to 7-mile walks, but they leave me exhausted afterwards, and my legs still seem small and flaccid. I was capable of running a (slow) half-marathon (13.1 miles) about 3 years ago. Now the weather is nasty and I'm not walking very often.

I'm isolating at home, where I have dumbbells that I've been too lazy to use and an elliptical machine that's buried in a room full of bins (my brother moved my stuff to my current abode while I was hospitalized and I haven't unpacked 95% of my crap).

I guess there's no point in taking the creatine if I'm not actively working on strength?! SHIT I need to get on that!

Thanks for the (unintentional) dope slap, Luis!

[-] luisvel | 2 points | Dec 26 2020 23:38:15

It can motivate you as you’ll surely see results faster than not taking it. Muscles also recover fast if you had them there. The bad called “muscle memory” is real and well documented 😎

[-] my-tech-reddit-acct | 2 points | Dec 28 2020 02:30:18

From this study of Medicell technology and cattle comes this image which shows the plasma level of ivermectin increasing after ~85 days after dosing and peaking around 240 days. MedinCell's tech is supposed to secrete ivermectin over time, which confuses things, but the apparent implication of the chart is that ivermectin stored in the tissues is released into the blood stream long after dosing.

Given the nature of the Medincell treatment, I'm not sure we can draw any conclusions about the plasma level increasing due to fat depot, as opposed to inconsistencies in the treatment depot.

[-] my-tech-reddit-acct | 1 points | Dec 28 2020 02:11:36

This is "reference 9" I referred to here: https://www.reddit.com/r/ivermectin/comments/kiok4e/covid_19_and_ivermectin_prevention_and_treatment/

Thanks for digging this up. Also, thanks to whoever posted it on scribd.

The paper refers once to ivermectin's "lipophylicity", but with no further clarification. And that paper only feals with short term pharmacokinetics of a single dose, so it's hard to understand the application to a months long prophylaxis routine.

Yet Aguirre and Hirsch do refer to it on their update regarding dosing. So I don't get it.

Many other papers refer to ivermectin storage in fat e.g. "Due to its high lipophilic nature, ivermectin is exten- sively distributed with broad volumes of distribution (Vd) in all species. It tends to accumulate in fat tissue, which acts as a drug reservoir" ( The pharmacokinetics and metabolism of ivermectin in domestic animal species Ara´nzazu Gonza´lez Canga *, Ana M. Sahagu´n Prieto )