[-] DZinni | 3 points | Aug 10 2020 20:33:48

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ Ivermectin is unlikely to reach the IC50 in the lungs after oral administration of the approved dose or doses 10× higher than the approved doses as a single dose. The approved dose of ivermectin alone has a low probability of a success in the treatment of cornonavirus disease 2019 (COVID‐19).

Meh, COVID19 is more than a respiratory disease. It affect the whole body. ACE2 receptors are found in many places, including the digestive tract. The virus has been detectable in fecal matter in significant concentrations. ~~From what I recall, ivermectin is poorly absorbed through the gut~~. This would mean the load in the gut would be much higher than elsewhere. I suspect a typical therapeutic dose is well above what an ED50 would be for the gut.

For Ivermectin to work (or any other potential prophylaxis), you only need to slow the replication enough for the bodies immune system to not become overwhelmed or overreact).

There is also another theory, that COVID is primary spread through a fecal-oral route. If we eliminate the virus in the gut, we would significantly reduce the chance of spread.

edit: I was wrong. For non-ruminants, Ivermectin has 95% bioavailability when administered orally. This is why we inject cows but give oral doses to horses.

[-] TrumpLyftAlles | 1 points | Aug 11 2020 22:21:58

There is also another theory, that COVID is primary spread through a fecal-oral route. If we eliminate the virus in the gut, we would significantly reduce the chance of spread.

Say whut?

Could you go into this a little, or give a link about it, please? I have never heard of this and would love to learn about it.

[-] DZinni | 1 points | Aug 12 2020 01:40:46

The theory is 17 years old with SARS 1. Here is a good summary of it.

https://www.smh.com.au/national/sars-outbreak-at-amoy-gardens-20030418-gdgmh4.html

And the theory continues for SARS 2 (Article from February 2020)

https://www.gastrojournal.org/article/S0016-5085(20)30282-1/fulltext

However, in more than 20% of patients with SARS-CoV-2, we observed that the test result for viral RNA remained positive in feces, even after test results for viral RNA in the respiratory tract converted to negative, indicating that the viral gastrointestinal infection and potential fecal-oral transmission can last even after viral clearance in the respiratory tract.

A fecal-oral route would explain mass spread in nursing homes and asymptomatic spread.

[-] TrumpLyftAlles | 1 points | Aug 12 2020 03:33:48

fecal-oral route

Thanks very much.

in more than 20% of patients with SARS-CoV-2, we observed that the test result for viral RNA remained positive in feces, even after test results for viral RNA in the respiratory tract converted to negative

So my covid-recovered son can pass the virus to me by using my bathroom. :(

A fecal-oral route would explain mass spread in nursing homes

Why? Don't they have private bathrooms? It's not plumbing, that's too idiosyncratic.

asymptomatic spread

Because my son isn't coughing at me, but he is filling the bathroom air with virus?

[-] DZinni | 2 points | Aug 12 2020 04:48:10

So my covid-recovered son can pass the virus to me by using my bathroom. :(

Potentially yes. There are a number of mitigations your home has.

You likely have high-efficiency toilet (but also non-power assisted). These toilets produce 15x less aerosolized particles as commercial flushometers (non-Tank). Source
Your toilet probably has a lid on it. Flush with lid closed or while sitting.
Bathrooms have exhaust fans. This makes it a negative pressure room.
The biggest risk of fecal-oral transmission is not aerosolized particles, but of direct oral contamination. Wash the hands. Maybe consider buying a bidet.
The virus being detectable does not necessarily mean there is enough of a viral load to transmit it.

Why? Don't they have private bathrooms? It's not plumbing, that's too idiosyncratic.

Nursing homes are full of people that can't take care of themselves. Many are not as mobile. Many are incontinent. Give them a virus that also gives them diarrhea and the rooms are now hazmat areas. After they sit in their own shit for a decent amount of time, have a nurse come in and clean it all up. Hopefully she does a good job of cleaning herself up, otherwise she will infect the next person she sees.

Because my son isn't coughing at me, but he is filling the bathroom air with virus?

I'm more worried about him not washing his hands properly and then making me a sandwich.

[-] TrumpLyftAlles | 1 points | Aug 12 2020 06:07:10

I'm more worried about him not washing his hands properly and then making me a sandwich.

HEY, how do you know my son?

I think our best strategy is stay virus free.

Thanks for the excellent bathroom amelioration list.

[-] pathfinder1980z | -1 points | Aug 10 2020 20:39:02

You sound like you’re completely guessing here.

[-] DZinni | 0 points | Aug 10 2020 20:57:49

Conjecture.

[-] DZinni | 0 points | Aug 11 2020 02:33:32

What is the purpose of reposting this study here, asking about our thoughts, and then immediately dismissing any comment on the study?

[-] pathfinder1980z | -1 points | Aug 11 2020 05:02:47

If I was rude that wasn’t the intention. I didn’t dismiss any comment. Just yours. I’m looking for informed views. Not WAGs.

[-] TrumpLyftAlles | 3 points | Aug 11 2020 18:22:20

This is the standard hit piece against ivermectin. The interest in ivermectin was kicked off by the Monash 48 hours study. It was accompanied in the journal by 2 letters, both making this argument. It has been made in 8-10 other articles, all of which have one factoid, CONCENTRATION TOO HIGH!!!, reminiscent of news coverage of one of the candidates during the 2016 Presidential election, if you were following that.

If you're interested, a couple months ago I wrote about a possible conspiracy against ivermectin here. I could write a lot more now.

Maybe I should?

Disregard.

[-] pathfinder1980z | 1 points | Aug 11 2020 19:54:28

Dang. I actually like how you did the research on those authors. I concur with your suspicions. What’s a good dose in your view? Don’t worry about citing evidence.

[-] TrumpLyftAlles | 1 points | Aug 11 2020 20:05:47

The standard dose is 200mcg/kg, which is what I'm taking twice a week, hoping for prophylaxis.

Here is an easy way to translate 200mcg/kg (or whatever dose you prefer) for your weight.

I am not a doctor and you should never take medical advice from me. Seriously.

[-] pathfinder1980z | 2 points | Aug 11 2020 20:11:33

Few of us are doctors I’m sure. But some of us can read those papers closely and that’s helpful. Thanks

[-] TrumpLyftAlles | 1 points | Aug 11 2020 20:17:12

Some of you are friggin' intelligent.

[-] stereomatch | 1 points | Aug 11 2020 20:00:14

Keep in mind ivermectin bioavailability increases by 2.5x if taken with a fatty meal.

The standard 200mcg/kg dose for 80kg person is 16mg - so 6mg x 3 tablets.

If you double that, or 4x that - you are getting closer to the levels in the Monash Univ study.

That is 4x times 2.5x - ie a 10x improvement.

Repeat that for a few days - as some studies have done (in Peru study gave 4 pills over 2 days and then repeated for those whose symptoms returned).

Plus in vivo ie in humans, the dynamics may be different. Especially if the case studies/anecdotal evidence is suggesting a rapid reversal of symptoms/dyspnea within 48 hours.

That may suggest that a persistent ivermectin presence may weaken the virus replication enough to give immune response a head start.

Also the anti-clumping impact of ivermectin that is conjectured from the molecular binding models may have benefits too - by reducing clumping of RBCs - red blood cells (virus is being seen as a binding agent between two RBCs).

[-] TrumpLyftAlles | 2 points | Aug 11 2020 22:23:19

If you double that, or 4x that - you are getting closer to the levels in the Monash Univ study.

I have tried and failed to understand how much ivermectin it would take to hit the Monash blood levels. Can you explain the math, please (again)?

[-] stereomatch | 1 points | Aug 11 2020 23:06:06

I have tried and failed to understand how much ivermectin it would take to hit the Monash blood levels. Can you explain the math, please (again)?

I think the Univ Monash study suggested the plasma levels needed to be 35x higher than the typical 200mcg/kg ivermectin dose (ie 16mg for 80kg person) to match their test doses (to get 50pct inhibition of virus).

However Adam Gaertner (interviewed by Dr Been and also by Dr Yo recently on ivermectin) in both interviews pooh-poohs the Univ Monash study as being misleading in it's conclusion that typical dose wont help.

The idea being that in vitro ie test tube it may be one thing, but in vivo ie humans it may have different effect or dynamics.

For example prolonged or repeat exposure to ivermectin may steadily chip away at the virus' ability to multiply.

Or as Adam Gaertner says, doctors are seeing improvement with even lower doses than the standard one time 200mcg/kg dose that is typical for anti-parasitic/deworming.

But even if one is to think about how a dose given in the real world could approach the higher dose mentioned ln Univ Monash study - you can see that in many studies they are given doses that are higher than 200mcg/kg - in some they give 600mcg/kg, while in the Peru study they gave 2x the 200mcg/kg dose and repeated it again for those whose symptoms recurred.

Multiply that with the 2.5x improvement in bioavailablility when taken with fatty meal, and you are seeing 2.5x times 2x or 4x - le as high as 10x - which gets you closer to the 35x ballpark.

Here is the 35x figure for the Univ Monash study:

https://www.news-medical.net/amp/news/20200427/Ivermectin-alone-not-useful-in-treating-COVID-19.aspx The approved dose of ivermectin alone not useful in treating COVID-19 Apr 27, 2020

Paper:

https://www.medrxiv.org/content/10.1101/2020.04.21.20073262v1 The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19 Virginia D Schmith, Jie Zhou, Lauren RL Lohmer doi: https://doi.org/10.1101/2020.04.21.20073262

Introduction: Caly, Druce (1) reported that ivermectin inhibited SARS-CoV-2 in vitro for up to 48 h using ivermectin at 5 uM. The concentration resulting in 50% inhibition (IC50, 2 uM) was 35x higher than the maximum plasma concentration (Cmax) after oral administration of the approved dose of ivermectin when given fasted. Method: Simulations were conducted using an available population pharmacokinetic model to predict total (bound and unbound) and unbound plasma concentration-time profiles after a single and repeat fasted administration of the approved dose of ivermectin (200 ug/kg), 60 mg, and 120 mg. Plasma total Cmax was determined and then multiplied by the lung:plasma ratio reported in cattle to predict the lung Cmax after administration of each single dose.

Results: Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations do not reach the IC50, even for a dose level 10x higher than the approved dose. Even with higher exposure in lungs than plasma, ivermectin is unlikely to reach the IC50 in lungs after single oral administration of the approved dose (predicted lung: 0.0857 uM) or at doses 10x higher that the approved dose administered orally (predicted lung: 0.817 uM). Conclusions: The likelihood of a successful clinical trial using the approved dose of ivermectin is low. Combination therapy should be evaluated in vitro. Re-purposing drugs for use in COVID-19 treatment is an ideal strategy but is only feasible when product safety has been established and experiments of re-purposed drugs are conducted at clinically relevant concentrations.

[-] TrumpLyftAlles | 2 points | Aug 11 2020 23:51:09

Required dose/kg = (35 * 200mcg/kg) / 2.6 = 2,692 mcg/kg

The Italy trial is dosing one arm at 1200mcg/kg, for 5 consecutive days.

The half-life of ivermectin is 18 hours.

Dang, I'm going to have to go figure out how to handle the half-life thing.

Thanks for the nice clear explanation!

[-] stereomatch | 1 points | Aug 12 2020 06:15:15

The 18 hour half-life of ivermectin is perhaps what leads to the repeat of dose after 1-2 days in some of the studies - like in the Peru study where if symptoms reappear they give ivermectin again for 2 days ie repeat. Then to repeat it again if still symptoms repeat.

It might be instructive to hear what the prophylaxis dose some doctors are recommending:

https://www.reddit.com/r/ivermectin/comments/i81t9s/_/ Trialsite interview of medcram (Dr Seheult) - section on ivermectin

we were using it in the hospital - still are using it in the hospital we give it one time - usually that is good for about a week (prophylatically for staff ?)

https://www.reddit.com/r/ivermectin/comments/i81wzl/_/ Dr Yo interviews Adam Gaertner - ivermectin, vitamin c

what he takes for prophylaxis takes 12mg once a week - 150mcg/kg

So they are using a 150-200mcg/kg dose per week. Which for an 80kg person means 12mg to 16mg per week.

Though by end of week it's effect in blood will be weaker. But I suppose they are aiming for if an infection happens at the end of the week or anytime - it is not more than 2-3 days away from an ivermectin peak in the blood.

[-] pathfinder1980z | 1 points | Aug 11 2020 20:12:18

I’m confused because I thought take ivermectin on Empty stomach?

[-] stereomatch | 1 points | Aug 11 2020 20:22:20

The pamphlet that comes with the tablets says that eating with fatty meal gives 2.5x bioavailability.

see below:

https://www.reddit.com/r/covid19/comments/hcpmxj/_/fvjdcsw

after high fat meal (not fast) - 2.5x increase in bioavailability vs fasted dosing

[-] pathfinder1980z | 1 points | Aug 11 2020 20:38:52

Could we take it on empty stomach with 2-3g of omega3? Need an efficient solution here

[-] stereomatch | 1 points | Aug 11 2020 20:51:44

Just take it with your usual meal.

[-] TrumpLyftAlles | 2 points | Aug 11 2020 22:25:38

This is a friendly sub. We shouldn't go around just assuming that everyone eats meals. Vampires, for example, are just as vulnerable to covid-19 as living people. Let's try to be open to differences.

!This is a rare attempt at humor. You can tell why the attempts are rare.!<