This is another CONCENTRATION TOO HIGH!!! paper (yawn!), which added two argumentsI don't recall seeing before:
93% of ivermectin is bound to plasma proteins that limit its cellular uptake by endothelial cells
"the total concentration of ivermectin in calves injected with 200 μg/kg reached only 100 ng/g (approx. 0.1μM) in lung tissue"
Yet more proof that ivermectin cannot be effective. /s
The letter starts at the usual place, the Monash 48 hours study. The six authors are from all over the world; one is at the Harvard T.H. Chan School of Public Health, Boston, a place I generally respect. It's interesting that this coalition came together to knock ivermectin. What is their motivation, to make an argument that was made in two letters accompanying the original Monash publication, and in 8-12 articles and papers since?
Edit: They make a couple suggestions that might be construed as positive:
Potential avenues for further investigation into repurposing ivermectin for SARS‐CoV‐2 may be to (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure and (ii) evaluate synergistic effects of ivermectin with other compounds that also inhibit SARS‐CoV‐2 replication.
Paragraph 1: Low-cost widely accessible drugs would be helpful.
P2: Monash 48 hours
P3: CONCENTRATION TOO HIGH!!!
Third, whilst there is no data on the tissue penetration of ivermectin in human lungs,
the clinical effects of ivermectin at a concentration of 5μM range are unknown and may be associated with toxicity.
These are things that are NOT currently known about ivermectin. The second excerpt is to scare people and put them off ivermectin.
P4:
some people may experiment with more concentrated veterinary formulations.
I'm unaware of more concentrated veterinary formulations. They present no information about them. Horse paste ivermectin is the typical 200mcg/kg.
These actions are not based on clinical trials and have motivated cautionary statements from institutions such as the FDA against the use of pharmaceutical formulations of ivermectin intended for animals as therapeutics in humans
Again, be scared!
P5:
Potential avenues for further investigation into repurposing ivermectin for SARS‐CoV‐2 may be to (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure and (ii) evaluate synergistic effects of ivermectin with other compounds that also inhibit SARS‐CoV‐2 replication.
Others have already thought of these ideas and are doing trials.
With 18 registered clinical trials (clinicaltrials.gov) evaluating ivermectin for the treatment of COVID‐19, this letter highlights the critical need to consider pharmacological principles to guide in vitro and clinical testing when repurposing old drugs for therapeutic use for the SARS‐CoV‐2 pandemic
There are at least 45 registered trials.
"[T]he critical need to consider pharmacological principles" is just a callback to P3 CONCENTRATION TOO HIGH!!!
Their point is not to knock ivermectin but to scientifically describe what is currently known about ivermectin.
CONCENTRATION TOO HIGH!!! is not a new idea. This is perhaps the 10th or 12th such article, making near-identical arguments. They add a bit to bolster the argument, "93% of ivermectin is bound to plasma proteins" and "the total concentration of ivermectin in calves injected with 200 μg/kg reached only 100 ng/g (approx. 0.1μM) in lung tissue".
Everything else in this letter is very well-known.
So the letter's net contribution is two more reasons why ivermectin won't work. It's just another hit piece.
Their point is not to knock ivermectin
What positive aspects of ivermectin did the letter describe? None, except faintly implying that it's cheap and widely-available, in the first paragraph, and there they didn't explicitly ascribe these attributes to ivermectin.
The rest of the letter knocks the drug.
but to scientifically describe what is currently known about ivermectin.
If you think this letter describes what is currently known about ivermectin, then you're a new-comer. Welcome! There is a LOT more known about ivermectin than is represented in this letter.
The larger thing to know is that this paper, like the other 10-12 like it, all start with the Monash 48 hours study. It is THE go-to for people attacking ivermectin. Monash is in vitro research, i.e. a test tube study. Everyone knows that in vitro studies seldom bear out in the real world so their results should be taken with a giant grain of salt. Nonetheless this result from an in vitro study is trotted out over and over, for the goal of knocking ivermectin.
Edit: I'll allow that their two suggested work-arounds for CONCENTRATION TOO HIGH!!! in paragraph 5 could be interpreted as positive.
[-] TrumpLyftAlles | 1 points | Aug 18 2020 22:41:23
This is another CONCENTRATION TOO HIGH!!! paper (yawn!), which added two argumentsI don't recall seeing before:
93% of ivermectin is bound to plasma proteins that limit its cellular uptake by endothelial cells
"the total concentration of ivermectin in calves injected with 200 μg/kg reached only 100 ng/g (approx. 0.1μM) in lung tissue"
Yet more proof that ivermectin cannot be effective. /s
The letter starts at the usual place, the Monash 48 hours study. The six authors are from all over the world; one is at the Harvard T.H. Chan School of Public Health, Boston, a place I generally respect. It's interesting that this coalition came together to knock ivermectin. What is their motivation, to make an argument that was made in two letters accompanying the original Monash publication, and in 8-12 articles and papers since?
Edit: They make a couple suggestions that might be construed as positive:
Potential avenues for further investigation into repurposing ivermectin for SARS‐CoV‐2 may be to (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure and (ii) evaluate synergistic effects of ivermectin with other compounds that also inhibit SARS‐CoV‐2 replication.
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[-] propargyl | 2 points | Aug 19 2020 05:05:15
Their point is not to knock ivermectin but to scientifically describe what is currently known about ivermectin.
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[-] TrumpLyftAlles | 1 points | Aug 19 2020 06:44:26
Are we responding to the same article?
Paragraph 1: Low-cost widely accessible drugs would be helpful.
P2: Monash 48 hours
P3: CONCENTRATION TOO HIGH!!!
Third, whilst there is no data on the tissue penetration of ivermectin in human lungs,
the clinical effects of ivermectin at a concentration of 5μM range are unknown and may be associated with toxicity.
These are things that are NOT currently known about ivermectin. The second excerpt is to scare people and put them off ivermectin.
P4:
some people may experiment with more concentrated veterinary formulations.
I'm unaware of more concentrated veterinary formulations. They present no information about them. Horse paste ivermectin is the typical 200mcg/kg.
These actions are not based on clinical trials and have motivated cautionary statements from institutions such as the FDA against the use of pharmaceutical formulations of ivermectin intended for animals as therapeutics in humans
Again, be scared!
P5:
Potential avenues for further investigation into repurposing ivermectin for SARS‐CoV‐2 may be to (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure and (ii) evaluate synergistic effects of ivermectin with other compounds that also inhibit SARS‐CoV‐2 replication.
Others have already thought of these ideas and are doing trials.
With 18 registered clinical trials (clinicaltrials.gov) evaluating ivermectin for the treatment of COVID‐19, this letter highlights the critical need to consider pharmacological principles to guide in vitro and clinical testing when repurposing old drugs for therapeutic use for the SARS‐CoV‐2 pandemic
There are at least 45 registered trials.
"[T]he critical need to consider pharmacological principles" is just a callback to P3 CONCENTRATION TOO HIGH!!!
Their point is not to knock ivermectin but to scientifically describe what is currently known about ivermectin.
CONCENTRATION TOO HIGH!!! is not a new idea. This is perhaps the 10th or 12th such article, making near-identical arguments. They add a bit to bolster the argument, "93% of ivermectin is bound to plasma proteins" and "the total concentration of ivermectin in calves injected with 200 μg/kg reached only 100 ng/g (approx. 0.1μM) in lung tissue".
Everything else in this letter is very well-known.
So the letter's net contribution is two more reasons why ivermectin won't work. It's just another hit piece.
Their point is not to knock ivermectin
What positive aspects of ivermectin did the letter describe? None, except faintly implying that it's cheap and widely-available, in the first paragraph, and there they didn't explicitly ascribe these attributes to ivermectin.
The rest of the letter knocks the drug.
but to scientifically describe what is currently known about ivermectin.
If you think this letter describes what is currently known about ivermectin, then you're a new-comer. Welcome! There is a LOT more known about ivermectin than is represented in this letter.
The larger thing to know is that this paper, like the other 10-12 like it, all start with the Monash 48 hours study. It is THE go-to for people attacking ivermectin. Monash is in vitro research, i.e. a test tube study. Everyone knows that in vitro studies seldom bear out in the real world so their results should be taken with a giant grain of salt. Nonetheless this result from an in vitro study is trotted out over and over, for the goal of knocking ivermectin.
Edit: I'll allow that their two suggested work-arounds for CONCENTRATION TOO HIGH!!! in paragraph 5 could be interpreted as positive.
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[-] LinkifyBot | 1 points | Aug 19 2020 06:44:40
I found links in your comment that were not hyperlinked:
I did the honors for you.
^delete ^| ^information ^| ^<3
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