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What’s Up With Ivermectin?

One of the small-molecule drugs that’s getting attention as a possible coronavirus treatment is Ivermectin, which is an interesting story from a couple of different directions. I’ve been getting some inquiries about it, so I thought it was time to have a look.

Background on Ivermectin

It’s part of a family of natural products called the avermectins, isolated (as have so many other interesting natural products) from soil actinomycetes. I go back quite a ways with this compound, back to my graduate school days when several folks in my old research group were trying to complete a total synthesis of the compound. It was (not so affectionately) known in the group as “Nevermectin”, which should give you some idea.

If you look down in the “southeast” of the molecule, you can see one reason it was no fun to make – the organic chemists in the audience will note that deconjugated enone (the double-bonded carbons that aren’t next to the carbonyl, but rather skip a carbon). As you might imagine, getting that thing in that position and (even worse) keeping it there was very annoying. The rest of the structure falls into the “doable with time and effort” category – the rest of the ring structure down there, the spiroketal in the northeast, the macrolide polyene ring, and the glycosyls coming off of it. The carbohydrate part is two oleandrose units in a row; I think that this is the most famous occurrence  of that otherwise obscure sugar. Ivermectin (and parts of it) have been synthesized several times since the 1980s by different routes, but like the huge majority of natural products, no one makes avermectin from scratch – it’s made by fermentation of the soil organism, which is far better at it than we’ll be any time soon. A related group of compounds, without the carbohydrates on the side, are the milbemycins.

The drug’s two main discoverers and developers won the Nobel in 2015 for it, deservedly so, because it has been a tremendous force in the campaigns to eliminate untold amounts of human suffering in river blindness and filariasis. (Merck, I should note, has donated the drug for those purposes ever since the late 1980s). The drug is effective against a wide number of parasites and arthropods in general- pinworms, mites, lice, heartworms and fleas in dogs, parasitic worms in pasture animals, as an ingredient in ant baits, and more. It acts most strongly on glutamate-gated chloride channels, which vertebrates don’t even have, although it can also bind to other ligand-gated chloride channels at higher concentrations. It’s really just an accident of pharmacology that it doesn’t cause more problems – it’s very toxic to a number of turtle species, for example, and to some particular breeds of dogs (particularly collies and other herding types). In both those cases it seems to be differences in the P-glycoprotein transporter proteins in the blood-brain barrier; that’s one of the key “toss this compound back out” proteins in many cell membranes. Turtles apparently don’t pump the drug back out at all, and those dog breeds have picked up mutations in PGP (all that close breeding) that allow the drug to accumulate in the brain and set off severe neurotoxicity via those other ion channels.

Ivermectin and COVID-19

So what is this compound doing in the news with the coronavirus? Its ion-channel mechanism of action against parasites has no application to viruses. But it has been shown several times to have activity in cell assays against Dengue infection and to reduce viral loads in the mosquito vectors (see this paper and references therein), although the reasons for this are still unknown. There have been some human studies for efficacy, but all I can find out is that a preliminary read showed no reduction of viral load in the infected patients, and there seems to have been no update. But since denguevirus is also a single-strand positive-sense RNA virus, Ivermectin has come up as a possible coronavirus drug, mechanism or not.

Here’s where the puzzling part comes in. A group at Monash Univ. showed a month ago that Ivermectin could inhibit the coronavirus in vitro. That paper is also a good review of the attempts at repurposing the drug in the antiviral space. The thing is, if you crank up the concentration, probably a lot of stuff will inhibit any given virus in vitro (relevant XKCD). The IC50 in their assay was about 2µM, and that number is where many medicinal chemists started getting off this particular boat. Micromolar cell-assay activity can certainly be real, but you’d generally want more potency than that as you move in vivo. The thing about Ivermectin is that it is effective against things like the river blindless parasite at really low doses: one 12mg or 18mg dose every few months. That’s not because it hangs around in the blood in high concentrations for that long – the compound’s half-life is a few hours, and it’s extensively metabolized as it goes through the liver. It does distribute strongly out into tissue, though, and that combined with its intrinsically high activity against the roundworms does the job.

But let’s imagine that you want to hit that 2 micromolar IC50 concentration in the bloodstream: how much Ivermectin would you need to take? Well, this calculation will involve some hand-waving, because who knows what the pharmacokinetics do as you head upwards like that. Here’s why I don’t want to even guess: that last link will show you that an 18mg tablet gives a peak blood concentration of 31 nanograms/mL. Ivermectin has a molecular weight of 875 (rather a lot when you think about it, to quote an old Monty Python routine), so that Cmax of 31 ng/mL is about 35 picomolar in the blood. Told you it was potent! So we’re around five orders of magnitude off here, which just isn’t feasible. One would have to hope that the compound concentrates significantly in the site(s) of action – really, really significantly. And we have no evidence that that’s happening.

It doesn’t take much to do these calculations – people were throwing their hands up in the air as soon as the Monash paper came out. As those letters to Antiviral Research note, ivermectin will start to hit other targets as you jack up the doses. The reason it’s such a great antiparasitic drug is that you don’t have to dose up at all. It’s hard to imagine that it’s a safe compound if you really have to push the concentrations to even within binocular distance of those in vitro levels. For that reason, the FDA has been warning people not to take the drug for the coronavirus.

Nonetheless, there is said to be a clinical trial in France getting underway investigating the drug, and just the other day one went up at That one looks odd to me in general – it’s an open label comparison in coronavirus patients of Ivermectin and the antiandrogen drug bicalutamide (which is given for prostate cancer). I simply have no idea what that’s about; if bicalutamide has been publicly suggested as a repurposed drug for the pandemic, I’ve certainly missed seeing it. Update: there are actually nine trials showing at ranging from Ivermectin along to things like Ivermectin plus nitazoxinide, which also seems futile to me.

A correspondent has sent me anecdotal reports from South America of people seeing efficacy with Ivermectin, but (as is usual with anecdotal reports) I don’t know what to make of those, either. At the normal doses of the drug (which is what those reports were doing, or perhaps 2x to 3x), it’s hard to see how any activity it might show would relate to the Monash study at all. I’m willing to wait to see some more controlled clinical data, but this really does look like the proverbial shot in the proverbial dark to me. I still have some hopes for repurposed drugs against the coronavirus, but not really in this case.

Update: see here for more on Ivermectin PK as regards coronavirus therapy.

Update: as per the comments, there’s work showing that Ivermectin apparently inhibits the actual of a different class of viruses based on inhibition of protein import into the nucleus. Could that be what’s going on here? Such a mechanism has been considered for antiviral therapy, but it’s in early stages of work.

Update: there is a report, using data from a company that has a real-time hospitalization database, of a retrospective matched-control set of coronavirus patients receiving Ivermectin versus those that did not. This analysis showed a pronounced effect in favor of Ivermectin, which is quite interesting. If this is real, it should definitely show in the other trials that are underway. More on this as data come in. . .Update: this company’s data-handling techniques have come under fire, and the report mentioned has been taken down, reasons unexplained.

147 comments on “What’s Up With Ivermectin?”

  1. Bell4 says:

    I think that’s supposed to be 35 nM.

    1. Some idiot says:

      Yep… roughly 30 ng divided by MW bit under 1000 is around 40 picomol per ml, therefore around 40 nanomol per l, therefore around 40 nmol

      1. Derek would like you to read Dr. Marina Bucar’s studies where she has pursued a protocol that reduced the mortality of covid patients from 18% to 1%. She separated the patients into phases and sub-phases and applied different remedies in each phase, curing them. She has all the protocols published on her instagram and will start to be released soon to all doctors in Brazil, please check I tried to translate but ididnt Because it’s like a photo.

        1. Ines says:

          I am not scientist or doctor but Yes! This Brazilian doctor says that the disease has fases and she treats every patient differently depending in the fase. I’ve heard from doctors in Brazil that the Ivermectin in the early stage of the disease works wonders. In case you get to the second fase (respiratory symptoms) the hydroxycloroquine inhibits the over imune response To the virus. After that the anticoagulants with antibiotics and cortisone reduces the severity if the last fase of the disease.

    2. Another idiot says:

      I had a moment of panic when I read Derek’s post.. had I been doing this calculation wrong for 20 years?!! I trust in Derek but my triple check says the right answer is nanomolar, not pico. Whew.

    3. Witold says:

      Yes, 35 nM ! Obvious error breeds misinformation.
      Also google the 1. Clinical trial ivermectin- Covid; it is ongoing with results due in early July, and 2. 60 patients recovered quickly in Bangladesh after a single dose plus the treatment with doxycycline. An apparent enrichment in tissue might by relevant here.

  2. Another caveat I’ve come across when using IVM at micromolar concentration in vitro in the presence of physiological saline is its tendency to precipitate (it’s visible under a x10 >2 microM in our hands in Ringers). A concern, then, is that some of these effects reported in vivo (e.g. cytotoxicity to cancer cells, or interference with viral infection) might be nonspecific effects of having aggregates bouncing around the culture dish bashing into and/or adhering to delicate biological membranes and whatnot. Easily controlled for, but I don’t think I’ve seen any of these papers do so.

    1. brain fart: that’s HEPES-buffered Tyrode’s not Ringer’s :/ (we see precipitate in KSFM culture media, also in the 3-10 micromolar range)

  3. Gustavo Aguirre Chang says:

    Ve have found that Ivermectin is very effective, what was reported in vitro in the Australia study carried out in early April, we have evidenced it when treating people with COVID-19.

    And we have managed to get its use approved in our country.
    More details at:

    1. Marco Lara says:

      Can a qualified professional please comment on Dr. Aguirre Chang’s post? He refers to positive results in the Dominican Republic, and Peru and refers to a paper: that seems very compelling. A doctor in Florida is also reporting good results with this drug:

      1. Roman Shein says:

        I’m not a professional and I wasn’t good in chemistry in school. At the same time I was good in math. I calculate that 1microM/L translates into a dose of 1.6mg/kg every couple of days to maintain sufficient concentration. The protocol from your link suggests 0.2mg/kg. It is an order of magnitude lower dosage and a concentration way lower than the needed 1microM/L.
        I wonder what is the rationale for the protocol then…

        1. Blaine White, M.D. says:

          There is an internet FDA report of ivermectin safety at 10X standard dose (SD = 12 mg = 4x 3 mg pills). A paper was also published in Ann Emerg Med reporting on ivermectin overdoses. In that paper it’s noted that no OD toxicity is seen below a dose of 20 mg/kg, and the reported death was at a dose of 100 mg/kg. Thus in general oral ivermectin appears to have little toxicity in the dose range that would be needed to approach a serum concentration of ~ 2 microM. It also has a fairly long circulating 1/2 life. Finally, the manufacturer reports alcohol ~doubles ivermectin absorption. So some “spirits frumenti” and 120 mg (10x SD) might do the job for a happy patient!

          1. Billy Bob says:

            You might want to check again, M.D.


            I’m all for poor nations and poor peoples of the world getting their due diligence practice in repurposed medicine.

            Johns Hopkins has ramped up the dosing protocol a bit. The dose could probably be higher, if you asked me. But who am I?

  4. Tim says:

    “(rather a lot when you think about it, to quote an old Monty Python routine)”

    For those who are curious, a quick literature search suggests two possible hits:

    (1) Salvation Fuzz, better known as the Dead Bishop on the Landing Sketch. One of their more famous ones, I think.

    Woman: Well there’s rat cake … rat sorbet… rat pudding… or strawberry tart.

    Man: Strawberry tart?!

    Woman: Well it’s got some rat in it.

    Man: How much?

    Woman: Three, rather a lot really.

    (2) The Insurance Sketch.

    Martin: Good morning. I’ve been in touch with you about the, er, life insurance…

    Feldman: Ah yes, did you bring the um … the specimen of your um … and so on, and so on?

    Martin: Yes I did. It’s in the car. There’s rather a lot.

    Feldman: Good, good.

    Martin: Do you really need twelve gallons?

    1. A Nonny Mouse says:

      I had thought that it was from The Life of Brian and what have the Romans ever done for us.

  5. cynical1 says:

    Yes, but did they test it in the presence of Zinc? Everyone knows that the oleandrose side chains and spiroketal forms a dimeric metal coordination site that serves as an ionophore for zinc! Gosh, don’t they know anything?

    BTW: Isn’t that an deconjugated acrylate and not an enone you are referring to? But I get your point……..

    1. li says:

      The oxygens coordinate Lithium ions better, which is good for many folks in this blog who seem to experience a manic episode

    2. Thank you! says:

      Aren’t you such a smart little boy. I hope the teacher gives you a cookie for properly chastising the nerdowells in the back of the class. This comment was so helpful in policing the proper bounds of discourse!!!

      1. loupgarous says:

        We have to chastise nerdowells? My God, man, our national defense and current search for a cure to Chinese coronoviremia depends on nerds who do well. Bill Gates has promised to build us seven vaccine production plants from money he made when Microhard stopped supporting Windows XP! Whatever you do, don’t chastise the nerdowells!

    3. Michael Broder says:

      Zinc is to coronavirus discussion as Spam was to Monty Python skits.

  6. David Young MD says:

    Well, there is a four arm study underway in Egypt, three of the arms including Ivermectin combined with another drug, with a completion date estimated to be in the year 2030. It is going to take 10 years to recruit 80 patients?

  7. David Young MD says:

    Then there is the University of Kentucky’s trial, another four arm, recruiting 280 patients, with one of the arms including Ivermectin combined with Hydroxychloroquine. There is a Hydroxychloroquine arm, a Hydroxychloroquine with Azithromycin arm and a Camostat by itself arm. Sort of a diverser four-armed study. The Ivermectin is just 12 mg days 1 and 2,…. that’s it.

    1. Mike Owens says:

      FYI (everyone) – Only proper nouns (e.g. trade names) are capitalized within sentences. None of the drug names above should be capitalized. Think as if you were going to capitalize water or oxygen within a sentence.

    2. Christine Carroll, PA-C says:

      So when the hydroxychloroquine/zithromyacin patients die from torsades arrhythmia, the ither drug regimes will look like winners!

    3. Rob says:

      What, no zinc.

  8. David Young MD says:

    One of the nice references for a criticism of the Australian paper can be found here. (start listening at about 16 minutes and it gets good at 18 minutes).

    If you look youtube and search Ivermectin you will find a number of physicians, from a variety of countries, who will claim that “Ivermectin was unexpectedly quite helpful in patients with Covid19”.

    There is a rational here:

    a) Because of the very low serum concentrations, Ivermectin should be ineffective.
    b) But we hear reports of anecdotal miraculous improvements
    c) Therefore we will study it.
    d) I suppose that it must concentrate in the lungs, and if I search long enough I can conjure up a reason why that might be so.

    (I am skeptical of the rational, just to let you know….. but I could be wrong, I suppose)

    1. austindude says:

      In ivitro studies on heartworm, The IC50 concentration it takes to kill heartworm is 8 micromoles (see page 10 on linked article) – about the same used to kill covid. Serum concentration is irrelevant because the drug breaks down so quickly, it is the corresponding tissue concentration that is important. We can’t reallly find out whether we have achieved a tissue concentration we need until we do the study but since such a high concentration is required to kill heartworm in vitro and the drug works to kill heartworm in dogs at a reasonable dose I think it very well could work.

      1. Erguen says:

        The article you linked (“Does evaluation of in vitro microfilarial motility reflect the resistance status of Dirofilaria immitis isolates to macrocyclic lactones?” Maclean et al., Parasit Vectors. 2017; 10(Suppl 2): 480., PMC5688452) does not even seem to have 10 pages in any common format? HTML is page-less anyway, PDF has 7 pages (with references), and in Pubreader format, page 10 is references.

  9. Chris says:

    Ivermectin may be anti-inflammatory and/or immunomodulatory via nicotinic receptors. It is mentioned near the end of this paper:

    1. loupgarous says:

      The discussion in Antiviral Research Derek pointed us to reminded us that ivermectin is also a nonselective inhibitor of three important mammalian P-type ATPases (SERCA, Na+/K+-ATPase and H+/K+-ATPase) at the same concentrations it took to disable coronavirus. Even the remnants of my education about how important oxidative phosphorylation swiveled my neck hard when I read that.

      Two letters to Antiviral Research in that discussion emphasize that when you’re potentially looking at giving much more ivermectin to people than anyone’s given before, and you know it inhibits enzymes important in oxidative phosphorylation in high enough doses, caution and constant patient monitoring are called for.

      1. loupgarous says:

        And all along, the toxicity issue with ivermectin in larger doses than previously given in humans isn’t what I thought it might be, but ivermectin’s action on GABA receptors. Issue’s discussed in a This Week in Virology discussion brought to our attention by David Young:.

    2. Jeffrey WA says:

      It would be interesting if its anti-inflammatory effect makes Ivermectin helpful. Perhaps the anti-inflammatory effect occurs at more acceptable dosages.

  10. LukasD says:

    Quite interesting is this observational analysis (nevertheless I cannot exclude data mining for some result):

    An international, multicenter, observational propensity-score matched case-controlled study using prospectively collected data on patients diagnosed with COVID-19 between January 1, 2020 and March 31, 2020.

    Results: The cohort (including 704 ivermectin treated and 704 controls) was derived from 169 hospitals across 3 continents with COVID-19 illness. The patients were matched for age, sex, race or ethnicity, comorbidities and a illness severity score (qSOFA). Of those requiring mechanical ventilation fewer patients died in the ivermectin group (7.3% versus 21.3%) and overall death rates were lower with ivermectin (1.4% versus 8.5%; HR 0.20 CI 95% 0.11-0.37, p<0.0001).

    Personally, I still have problems believing this paper.

    1. David Young MD says:

      Like anyone else, I have trouble with the participants not being randomized and it not being a prospective study. We all know the trap that one can fall into. The comparison group goes back to January first. Perhaps ICU treatment has improved from January 1st to April 15th so that the comparator arm was naturally going to do worse. Give Benadryl to the treatment arm from April 15 to May 3rd and perhaps they would have done better than historic controls as well. The bottom line is…. _it is really, really difficult to believe that just two tiny doses of Ivermectin is going to reduce the fatality rate from 21 percent to 7 percent_

      1. Hoyt Nelson says:

        DId you LOOK at the study? Overall fatalities were 5/6ths lower, fatalities among those on ventilators were reduced by two-thirds.

        Yet, it’s not a RCT, but those results are profoundly positive.

        1. David Young MD says:

          I don’t consider them “profoundly positive”. I think that it is very possible that this study is severely flawed in making comparison to outcomes in the past 3 weeks compared to outcomes several months ago. And there may be severe selection bias on who ended up getting ivermectin. If you are already on a ventilator it is hard to swallow an ivermectin pill. I am not impressed with the study, no matter the difference in outcomes. This is the same problem with the Didier Raoult study.

          1. Joshua Goodman says:

            Just wanted to say thank you, I’ve been fascinated by that study for a while, and was wondering if there is an explanation for how the results might be spurious. I appreciate your insights insights.

          2. Tim says:

            What about the doctors from Bangladesh who have seen remarkable results using Ivermectin along with Doxycycline?

          3. Bryon Wasserman says:

            There have been some anecdotal results from a few different places (Florida, South America, Bangladesh, Dominican Republic) of doctors having good results with Ivermectin. I don’t know how reliable these reports are. There are now *thirteen* Ivermectin trials in the FDA so I wonder if this is an attempt to validate these anecdotal reports. It may just be that Ivermectin is so cheap and widely accessible that they’re testing it as a low probability/high upside effort.

    2. Erguen says:

      The positive ivermectin study (Patel et al., Usefulness of ivermectin in COVID-19 illness. was done by the same authors and using the same methodology as the negative hydroxycloroquine study recently published in Lancet [Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis., which everyone is believing, and which made WHO and Sweden stop their hydroxycloroquine studies.

  11. Simon Auclair the Great and Terrible says:

    Well, I guess everyone is going with emotions, hope, and luck anymore…I can remember science anyway.

    Whats up with remdesivir btw? Anyone?

    1. David Young MD says:

      I am sure that Gilead is working as best it can to produce more drug. I understand that Gilead is contracting with other manufacturing centers to join in the effort. I would hope that every week that goes by will bring us lots more Remdesivir. Maybe in 4 weeks there will be plenty to go all around.

      1. David Young MD says:

        In fact, just yesterday there was news that Gilead contracted with about 5 other pharma manufactuers to make Remdesivir. Smart move, to make the supply ample.

  12. Christophe Verlinde says:

    What’s going on in the brains of the folks who run these ivermectin trials? Did they never bother to check on the lit. on blood concentrations of the drug. If Derek could do it in seconds they could have. Come on, when the IC50 (in vitro) is 5 orders of magnitude larger than the blood concentration, the decision to pursue trials borders on the belief in religious miracles. Who reviewed these trial proposals?

    1. Carlos Weaver says:

      2 muM/35 nM = 57, not five orders of magnitude

  13. Simon Auclair the Great and Terrible says:

    BTW I just took ivermectin prophylaxis for Baylisascaris after cleaning up after raccoons.

    And u don’t THINK I have covid 19!

  14. Simon Auclair the Great and Terrible says:

    Chris thats what I meant by emotion….

  15. Ted says:

    I recall spending time a few years ago looking into improved loaisis diagnostics. The reasons were interesting, although some of the research seemed loose. The premise is that widespread treatment with Ivermectin for Onchocerciasis was confounded by patients that carried comorbidity with loaisis. If you didn’t screen those patients out, Ivermectin (or more likely, the massive die off of parasites in the CNS…) therapy is associated with encephelopathy. It’s the kind of thing that could be readily managed by a clinician in a wealthy country, but the kinds of places where these problems are manifest need one-shot treatments with limited follow-up opportunities.


  16. Hoyt Nelson says:

    There are 9 trials of ivermectin underway. Two of them will look at ivermectin alone, the rest are ivermectin + something else.

    1. Derek Lowe says:

      Updating the post now. . .I have no idea why I didn’t get those on my own search! Thanks. . .

      1. John Wilkens says:

        I am not a chemist and I am way out of my element here, but based on some of those trials it looks like they will be administering anywhere from 200mcg – 600mcg/kg. All the way up to 60 mg total a day. You stated that the normal dose of 12 mg to 18 mg wouldn’t provide enough blood concentration to be effective, something like 5 times the amount less than needed. But wouldn’t a 60 mg dose provide 5 or at least ~ 3.5 times as much concentration? Or does it not work like that. Also, why is 60 mg the max…is it proven unsafe at levels higher than that?

        I’m curious to hear more about these studies, expecially the one in India that looks like it began on April 25th.

        1. John Wilkens says:

          Nevermind. I’m an idiot. I just re-read what you wrote and saw that it was 5 “orders of magnitude” less. Yea, that makes me much more pessimistic regardless of the dose they administer.

          1. Derek Lowe says:

            No problem. Yeah, it’s not the kind of gap one is used to seeing!

          2. KazooChemist says:

            Derek: what about the comments made earlier regarding the concentration? Which is correct? Are we off by five orders of magnitude or only a factor of fifty? Time to break out my calculator.

          3. David Young MD says:

            About 5,000. Listen to the scientist speaking starting at about the 18th minute:


          4. KazooChemist says:

            David: I listened to that the first time you posted it. The individual speaking at that point in the recording is talking about how you would go about dose escalation in a clinical trial basically addressing safety. I don’t see how that refers to the question of the math. Can you direct me to some specific point in the audio that addresses the required serum concentration suggested by in vitro studies relative to the data Derek provided regarding actual drug concentrations. Several posters have questioned the position of the decimal point.

          5. Some idiot says:

            Derek has now corrected it… Yep, around 50-100 fold difference. Still big, but still… As (I think it was) Barry mentioned, if there was local upconcentrating, then that would make a significant difference. How and why? No clue. But (again from Barry?), if it were possible to image it, that would be cool…!

            Roll on RCTs, so we can see if there is anything in this or not…! I think that David Young’s objections are pretty strong…

  17. ScientistSailor says:

    “Nevermectin” I love it. I was in a group that was working on the synthesis of Ouabain and Sarain A. We called them the “Ouabain of our existence” and “Sarain’t going to happen” Sarain was eventually finished, Ouabain, not so much…

    1. Anonymous says:

      Not a molecule, but “Diene Synthesis” by Andreĭ Sergeevich Onishchenko is a classic reference work. The boss let me borrow his copy, but I eventually got my own copy. Anyway, it was referred to by some of us as “Onishchenko mal y pense.” (Honi soit qui mal y pense. Shame be to him who thinks evil of it.)

      (I also worked in an avermectin group. Good times.)

  18. Barry says:

    Volume of distribution for Ivermectin is variously reported from 1.2 to >17 liters/kg. So when it’s 35nM in plasma, it must be far more concentrated somewhere else–potentially in the target-tissue, whatever that is.

    1. Derek Lowe says:

      Reports are that it’s in lipid depots (logP and all), for what that’s worth.

      1. Barry says:

        But it might also be concentrated in some organ (or organelle, or droplet) of the parasite

      2. Barry says:

        If we’re lucky enough to have a good fluorophore in the drug substance, I suppose we can localize it down individual organelles. Barring that, it’s still really really hard to know the local concentration at the target.

  19. Lane Simonian says:

    My guess is that for something to be effective against the coronavirus after viral infection it operates something like this:

    Getting from here to there, though, is going to be a major challenge.

  20. rtah100 says:

    A plea from the pedants’ row – it is orders or magnitudes, not orders of magnitude. In dimly remembered mathspeak, a magnitude is arithmetic, it is a change in a value by one power of x in base x; an order is functional analysis, it is the behaviour of a function (e.g. Equilibria) in the limits:
    – 100 is a magnitude bigger than 10; – O(n!) is (rather a lot!) bigger than O(n).

    It’s like saying feet of equilibrium. It makes no sense.

    1. KazooChemist says:

      Interesting. Never heard it described that way. Googling seems to show orders of magnitude as the proper plural and defines the meaning like everyone seems to use it. I’ll have to dig into it a bit deeper. Plenty of time during the lockdown to learn something new!

  21. Chris Phoenix says:

    Re anti-androgens – men seem to get COVID worse than women. And I haven’t seen statistics on whether obesity-without-diabetes is a risk factor, but it doesn’t look like as much of a risk factor as the media keep saying – and fat cells make estrogen (converting it from testosterone).

    Is estrogen protective? Is testosterone bad? It’s not completely crazy to think that tweaking androgen levels might have some effect on the disease. Of course, there may be a sweet spot, so I’d think you’d need to get hormone levels before and after treatment and analyze for their effects on outcomes – which means a pretty big trial/study.

  22. georgi momekov says:

    even with excessive doses the virus-inhibitory levels are an elusive goal, not to mention the fact that the drug is 93% protein bound

  23. Thomas J Boyer says:

    The only possible flaw in the can’t-hit-dose argument is that the drug might be helpful at much lower concentrations. The original in vitro study didn’t seem to explore that question.

    I think the thing to keep in mind here is — the bar for success is not “cure,” it’s not “wiping out virus in 2 hours.” The bar for success right now is ANYTHING THAT HELPS EVEN A LITTLE.

    And while we’re on that subject, retrospective study released today by team at Raymond Poincare university hospital in Paris — HCQ/ACI reduced the number of patients dying or ICU by 68 percent. SIXTY EIGHT. These were hospitalized patients and, like NY, sicker than the control group. Interestingly, AZI by itself delivered almost as great an improvement in outcomes — which Dr. Lowe may find interesting. Maybe the key to the Marseille protocol isn’t the HCQ, it’s the AZI…..

    I’m sure the Poincare paper will be ignored in the US by a scientific community that’s emotionally invested in seeing HCQ fail, and also because there’s no $100 billion California biotech out there going to lobby Washington on behalf of a 6 cent pill.

    1. WustMed says:

      Would you post a link? Like to see the data

    2. Adrian Green says:

      The UK recovery trial has provided some clarity. 1542 patients randomised to HCQ arm, one of which is Hydroxychloroquine. The have looked at this HCQ group in light of the recent concerns and have noted it(HCQ) is not effective.

      They conclude “These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19.”

  24. Jeffrey WA says:

    Some info with regards Androgen Deprivation Therapy and coronavirus.

    1. Barry says:

      I don’t know that the two are strictly comparable. But yes, we should offer castration to those who can’t bear to be seen masked in public.

  25. Andre Faria says:

    Hi Derek, I would guess that probably the french study in association with bicalutamide has something to do with this observational study recently published at Annals of Oncology:

  26. Joe Psycho says:

    What about remdesivir, favipravir, ribavirin, lopinavir+ritonavir, low dose HCQ and vitamin supplementation if needed(vitamin deficiency has been shown to be a risk factor). Just another idea.

  27. Alex says:

    There’s another trial dosing ivermectin by means of a nebulizer, this might get around the high dose required by going thru the blodstream….im guessing… would this replicates the in vitro process used to administer this drug by the Australian institute??

  28. Joey1849 says:

    I would be interested to hear what the posters here think about Ivermectin delivered by nebulizer directly to the lungs, thus avoiding the blood concentration issue.

  29. This link discusses the dosage disparity between approved use vs covid-19 requirements fairly well.

  30. fritz schomburg says:

    Considering there are indications that parasitic load suppresses the immune system, and many people harbor worms and don’t know it, it seems likely there may be an actual mechanism, albeit in people with a parasite load they don’t know about.

    Perhaps a better and first test would be to correlate the outcomes with parasite loads in the gut of patients.

  31. Chris Swain says:

    An interesting weekly podcast that is currently topical.

    This week Doris Cully joins TWiV to discuss inhibition of SARS-CoV-2 in cell culture by ivermectin.

  32. Former Merckoid says:

    Avermectin brings back fond memories of my days at SchMerck. My first task (in 1988) was to sequence the genes for the aglycone portion of the molecule. That was back in the day when I had to use 35S-dATP and pour two polyacrylamide sequencing gels per day, run them, clean up and pour two more for the next day. Got a whopping 200 base pairs for each run on a good day.

  33. The Science Mechanic says:

    We give our dog Heartguard Plus, whose active ingredient is ivermectin, for heartworm prevention. I checked the label and it doesn’t contain any breed-related warnings. The sensitivity is well-documented. The drug is only by prescription so perhaps this is handled at the veterinarian level? Are there black box warnings for veterinary drugs?

    1. Derek Lowe says:

      The package insert does have the warning about breed sensitivities, particularly mentioning collies:

      1. The Science Mechanic says:

        Damn, my poor fine-print reading skills! Thank you.

        Although I can see why there is not a more bold warning; it’s safe at the recommended dose and has a fairly big window:

        “Studies with ivermectin indicate that certain dogs of the Collie breed are more sensitive to the effects of ivermectin administered at elevated dose levels (more than 16 times the target use level) than dogs of other breeds. At elevated doses, sensitive dogs showed adverse reactions which included mydriasis, depression, ataxia, tremors, drooling, paresis, recumbency, excitability, stupor, coma and death. HEARTGARD demonstrated no signs of toxicity at 10 times the recommended dose (60 mcg/kg) in sensitive Collies. Results of these trials and bioequivalency studies, support the safety of HEARTGARD products in dogs, including Collies, when used as recommended.”

  34. Bijal Rawal says:

    What if Ivermectin is given via inhaled route ? This will A) achieve higher concentration (in microM) at the desired site of action and B) avoid systemic side effects.

  35. richard moore MD says:

    Ivermectin-yet it persisted

  36. leer says:

    If this is such absolute snake oil, how is it that Ivermectin works against porcine pseudorabies virus? Granted we’re not pigs, but…

    1. Derek Lowe says:

      That looks like an effect on a nuclear localization signal, but I wasn’t aware of that. Thanks – I’ll add this to the post.

  37. JP Leonard says:

    @cynical1 wrote: “Yes, but did they test it in the presence of Zinc? Everyone knows that the oleandrose side chains and spiroketal forms a dimeric metal coordination site that serves as an ionophore for zinc!” Really?
    One doctor does claim “remarkable” results with Ivermectin added to the HcQ+Zpak+Zn 3-pack. I cited him here at bottom of page. He heard about it from the Monash study. Don’t know the dosage. His county health board has approved his protocol.
    Your note is more like something nobody knows. Doesn’t come up on a google search. Maybe something to do with this? Or you just having fun

  38. Jerry Valdez says:

    I don’t understand why people write on broadsheets without a thorough review of the extant literature. That experiment in Monash is old age. There’s a newer study:

    There it was tried IN VIVO and it was only administered once!

    1. David Young MD says:

      Too good to be true. They could have given aspirin and achieved the same results. It was not a randomized study. They compared people who, in recent weeks, have received Ivermectin to another group, of equal size that involves people who started getting ill back in January. Is it possible that in the past 10 weeks that the supportive care treatment may have improved? Something to consider. At any rate, the two groups were not comparable (anyone who understands medicine would understand that). So, can you derive anything from that report? Nope.

      1. Erguen says:

        The same authors, using the same methodology, did the negative hydroxycloroquine study recetly published in Lancet ( and widely considered “damning”. Should that one be dismissed as well then, on the same grounds?:)

  39. blobo says:

    from my understanding ivermectin works by inhibiting the importin alpha/beta mediated nuclear import of viruses into the host cell. I don’t know about doses. but it makes sense to me that maybe you won’t need too much.

  40. Georgi Momekov says:

    The viral cargo import inhibitory mechanism requires pharmacokinetically impossible high micromolar concentrations:
    …Ivermectin was found to strongly inhibit the binding of Impα/β1 to NS5 (IC50=17 μM)…

    1. These are also supersaturating ivermectin concentrations for culture media, too. In addition to complicating interpretations of apparent IC50s, the prospect of this stuff coming out of solution at supposedly effective concentrations does dampen the enthusiasm for direct lung delivery approach suggested elswhere (without some sort of vehicle to offset the problem, I suppose).

      As it is, prior to the antiviral argument for ivermectin’s repurposing there’s been the anticancer one that has lauded ivermectin for its cytotoxic effects at these concentrations. It’s curious that these antiviral investigations are admitting to no such apparent cytotoxicity to the host cells.

  41. Nori Suzuki says:

    This article missed three new developments.
    1. Gates foundation paid $19M to a French company Medincell for clinical trial.
    2. University of Utah investigated 1400 cases of Ivermectin trials in the world of which 700 is
    patients administered Ivermectin and 700 patients nothing. The result is 6 times more death
    rate for patients with no medication.
    3. Dr. Ohmura, the Nobel laureate and the inventor of Ivermectin, has started the clinical trial
    of Ivermectin at Kitasato Lab in Japan.

    1. JP Leonard says:

      Thank you, Nori!
      1. Re Medincell, their project is subcutaneous injection of a pool or deposit of medicine that serves as a long term slow release delivery system. (No wonder vampire Bill Gates is interested)
      2. This appears to be the trials by Dr Patel here
      3. The trial is in planning phase.

  42. Catherine BerkMan says:

    Hi I am not a doctor but recently there was some data published with respect to data from clinical trials using ivermectin of which the results proved to be very effective.

    Here is the link

    From a lay persons perspective It feels like the powers that be are pushing for a vaccine. Both the FDA & CDC look to be in disarray.

    If this common drug can be effective in stopping covid as other MD’s have indicated, what on earth is the hold up in general availability to the public for use with covid-19 ?, like aspirin or another over the counter drug.

    Look folks the building is burning down fast. The lure of water from the pond across the hill is not going to solve this problem (Vaccine) because the fire will have completely burned the building down by the time the water arrives !!!!!!!!!!!!

    Thank you

    1. Derek Lowe says:

      The article that video references is linked in the update at the end of the post.

    2. Barry says:

      The preference for a vaccine rather than a therapeutic drug is not an arbitrary bias of “the powers that be”. A vaccine is a better solution. On one hand, a vaccine offers the prospect of eradicating the disease (as we achieved w/ e.g. smallpox). On the other hand, prevention (vaccination) is more efficient than treatment. Vaccination can be done in the village, worldwide. Treatment requires the expense of diagnosis, and of hospitalization.
      In all of Infectious Disease, there are only three bargains:
      -Potable Water
      -Sanitary Sewers
      Everything else is vastly more expensive, and can only be a stop-gap until we achieve these three where they are possible.

      1. Former Merckoid says:

        Hi Barry-

        If a vaccine is developed for SARS-CoV-2 the disease may not be eradicated as there are probably animal reservoirs for this virus. The smallpox virus (variola) was eradicated because there are no animal reservoirs – its solely a human pathogen.


        1. Barry says:

          You’re right, of course; strict eradication is possible only when there is no wild reservoir (or where you can vaccinate that reservoir, too). But transmission of this coronavirus from the reservoir to humans is very rare. That’s different from e.g. influenza that we swap back and forth with our pigs and poultry.

      2. JP Leonard says:

        Barry, the great majority of coronavirus patients are not hospitalized, and the point of having a good medication is so they won’t need to be hospitalized.
        Catherine Berkman’s point was not whether a cure or a vaccine is better, it’s that “the house is burning down” – meaning the lockdown is causing enormous damage, each day it continues the more permanent that damage will be, many small businesses will never re-open. Our national debt burden is skyrocketing. We simply can’t wait a year for a vaccine – especially when a lot of commentators doubt whether a vaccine is even possible for this one. I share Ms. Berkman’s sense of urgency about putting these promising treatments front and center into widespread use. Enough fiddling while Rome burns.

        1. JP Leonard says:

          “A bird in the hand is worth two in the bush.” You can’t compare what you have that is already working now, with what you might have someday that might work — certainly not in an urgent life and death situation.

  43. Kate Gahan says:

    No science background here but when the Monash study first made the news, I looked up which countries take Ivermectin for River Blindness and checked their mortality rate for C19. Unless these countries are not reporting properly, most of them have low rates of C19 deaths relative to other countries. I have no idea if that means anything but I thought it was interesting.

    1. Georgi Momekov says:

      You may also check the number of tests these countries have performed and the median age of their populations.

  44. Roman Shein says:

    Just my 2cc regarding “ivermectin… just isn’t feasible”.
    IC50 suggested by the paper (1mcM) translates into a single dose of 1.6mg/kg, which bring us to 120 mg dose for an average adult.
    There was a RCT Phase 1 (safety), testing 30 & 60 mg every 4th day, 90 and 120 mg (40 tablets of 3 mg each) single dose. There was no difference with placebo group (

    The veterinary grade ivermectine (the drug is not registered for humans in my country) costs 1 USD for 100mg.

    So far, in terms of safety and costs the drug looks feasible.
    Furthermore, the drug is widely used in the veterinary. The manufacturing capacity is scaled to supply drug for billions of domestic animals.

    I know for sure that the local veterinary drug is safe and effective (tried and tested on my mom, the drug is a magic bullet for her demodex).
    We all have seen how industrial face mask and even ordinary bandanas became “medical devices” overnight, unverified tests allowed for wide usage, hydroxycloroquine and others fast tracked for coronavirus. I wouldn’t be surprised if “non-suitable for human” grade ivermectin, suddenly become absolutely “approved”.

    1. Georgi Momekov says:

      The IC50 is not 1 microM, it ranges 2.2-2.8 micromol/L depending on the assay conditions. The Cmax from the study of Guzzo et al you have quoted is 247.8 ng/ml= 283.2 nmol/L.

    2. jem says:

      Which vet product did you use? Drench for sheep or cattle or for birds
      AS far as I can see the sheep drench is exactly the same dosage ad for humans .08% which ends up delivering 200 micrograms per kilogram which is to say 1ml per 4 kg.
      What si not clear is what is used for the solvent. Ivermectin is not soluble in water but is in ethanol and methanol. Not sure about NaCl though. It could be just salt water
      (cheapest option if viable) but the data sheet does not say.
      Would the exMerck person know..?

  45. Ruud van Ballegooijen says:

    Why everybody’s focusing on Ivermectin instead of Niclosamide, i’ll never find out, i guess. Watch this on YouTube:

  46. Ruud van Ballegooijen says:

    Look at you all being so smart with your $20 calculator, made in China…

    1. Bryon Wasserman says:

      Sorry-my comment somehow didn’t get pasted in. The link above is another reports from doctors in Indonesia claiming that they’re seeing lots recoveries from patients taking Ivermectin. Between the Peru doctors, the doctor in Broward and this, this is at least three independent places where they’re claiming success with Ivermectin. I wonder (hope) if the big spurt of randomized trials that popped up is a result of others seeing these kinds of results and trying to validate them.

    2. Bryon Wasserman says:

      In Bolivia they’re mass-distributing Ivermectin to treat Covid

  47. Erik Dienemann says:

    I assume you’ve seen the Morshed “article” from Bangladesh, claiming ivermectin + doxycycline (antibiotic) was effective in “curing” 60 COVID patients. Large grain of NaCl required for this one, but for me it would be really cool if ivermectin worked. In my early days at Merck (late 80s) I worked on evaluating manufacturing scenarios (it’s a bitch to make as you said), plus I was involved in doing some aquatic tox studies for environmental impact from application to livestock (it’s highly toxic in the aquatic environment to daphnia and other invertebrates).

    1. jem says:

      what does “Large grain of NaCl required for this one” mean please?

      1. Derek Lowe says:

        That refers to an English-language expression: to say that a statement “should be taken with a grain of salt” means that one should be skeptical about it.

  48. M Alam says:

    Bangladesh Police Hospital, Dhaka is also finding success by following Dr. Tarek Alam’s COVID19 treatment guideline. Police is the most affected professionals in Bangladesh, usually the hospital releases 20-30 patient cured everyday, but for the last 5-6 days they are releasing around 100 patient per day who are treated with Ivermectin+Doxicycline. Ref:

  49. Ron Conte says:

    bicalutamide was found to be effective as an inhibitor of RdRp (docking score -8.7) by:
    Gul, Seref, et al. “In silico identification of widely used and well tolerated drugs that may inhibit SARS-Cov-2 3C-like protease and viral RNA-dependent RNA polymerase activities, and may have potential to be directly used in clinical trials.” (2020).

    1. drsnowboard says:

      In silico calculated binding affinities are not proof of anything, least of all efficacy.
      Where’s the positive control in that paper?

  50. Jamal says:

    The drug is already yielding very positive results in Bangladesh. The writer should have known about it. Google it.

  51. shubh kharbanda says:

    There is a report in media where a doctor in Bangladesh has treated 60 patient with ivermectine and Doxycycline .
    How true is that?
    Here below is the link.

  52. T. V. Rajan, M.D. says:

    Am I missing something, or are some of the calculations here a little bit off? If the molecular weight is 875, then 875 nanograms/ml is 1 micromolar. To achieve 2 micromolar concentration, (1750 nanograms/ml), obe would need about 50 times the standard dose of ivermectin.

  53. Gopal says:

    Seems in Bangladesh, Ivermectin in a single dose with Doxycycline, an antibiotic, yielded virtually the near-miraculous result in curing many patients with severe COVID-19 with almost 100% cure rate. Can this be checked.

  54. Kazi Jamil MD, PhD says:

    Ivermectin is too important to be ignored and more research should be initiated to reap the benefits of having a cheap and safe means to deal with Covid-19 while the world awaits development of more effective drugs and vaccines. Johns Hopkins University is about to start a clinical trial on ivermectin using a dose of 600 microgram/day for 3 days (posted in Unfortunately the findings from the in-vitro study in Australia raised flags for the wrong reasons because the mechanism of action of ivermectin that we need to focus is not its direct killing effect on the virus. Basic research on the mechanism of action of ivermectin in the cell culture and animal model should be investigated urgently. It is no wonder that big pharma and investors would show little interest in a drug like this after the patent is gone.

    1. Hoyt Nelson says:

      Hopkins dropped the ivermectin arm of their trial. I emailed one of the researchers asking why, got a polite response that didn’t answer the question, and she didn’t answer at all when I emailed a second time pointing out that she hadn’t answered the question. Frustrating.

  55. Gene P. says:

    Thanks for this article and the comments from intelligent, trained, knowledgeable, experienced professionals. I’m a layperson who’s trying to grasp as much of it as I can, and I appreciate your efforts.

    I’m embarrassed for the posters of the comments about the findings of Dr. Youtube and Dr. Google, what the nefarious “powers that be” are up to, etc by credulous people who are clearly light years out of their element, yet somehow manage to believe they are contributing while in fact polluting these comments with their nonsense. You are all very kind to expend any energy at all on pointing them toward facts and reality, or by politely ignoring them. The humorous comment up top about how to treat those who can’t handle wearing a mask likely applies to them.

    1. Alex says:

      ….and your contribution to this blog is…..🤔

    2. Alex says:

      At least first of many trials results are coming out.
      The ICON trial at several hospitals in south Florida

  56. Lu Chen says:

    Today, the preprint (Patel et al., Usefulness of ivermectin in COVID-19 illness. was removed. It left behind fake hopes with 18 clinical trials and a 404 code.

    There is a nice archive & review about the Ivermectin preprints (2 versions) (

  57. M C CROWTHER says:

    I have been reading this article and everyone’s comments with great interest. I rescue horses and the wormer recommended by my vets was one that by my observation was more likely to kill very poor animals with a high worm burden. Ivermectin produced far better results. This was true even when they were also ill with suspected salmonella and with protein losing enteropathy. Consequently, I gave great fondness for ivermectin and was delighted to hear that this drug could be repurposed for treating coronavirus.
    Since ivermectin had been handed out in Bolivia, does anyone know if results are starting to come in?

  58. Jim Dowling says:

    A new (non double-blind, N=280) study on hospitalized Covid-19 patients from JJ Rajter in Florida is out with statistically significant reductions in mortality (15.0% versus 25.2%, OR 0.52, 95% CI 0.29-0.96, P=.03). Very interesting that it works is such late stage patients and gives hope of even greater efficiency when treated earlier in the course of the disease:

    1. Lu Chen says:

      In this study, the mortality of the control severe group is 81% (21/26), which is unreasonably high. Most likely they are extremely sick patients.

    2. Alex says:

      Interestingly very similar results to the ICON trial

      1. Hoyt Nelson says:

        It’s the same trial.

  59. Adel sakr says:

    Best way to have a high concentrate in lung tissue is through inhalation tech ….

  60. Kellie says:

    They don’t want any old cheap drugs to be the cure. Where is the money in that? They want to push their vaccine.

  61. Major pissed says:

    So where are all the know-it-all MDs (who are probably secretly using HCQ and Invermectin prophylactically) and grand-juror scientists that were mocking the effectiveness and relevance of this drug in early May? They should at least have enough dignity to come back here and admit there were wrong…or at least hastily judgemental.

    Good thing many of the poor people cured and saved by Ivermectin in Peru, Brazil, Dominican Republic etc were not knowledgeable enough to have their “all knowing wisdom and self-grandiose stand in the way of pursuing an “anecdotal” snake oil!

    1. loupgarous says:

      Da, da. Is good thing we don’t step in it!
      Da – let’s go eat!
      Da, go eat!

  62. Alfred Toledo says:

    Hi Mr Lowe,
    I live in Dominican Republic and there seems to be some independent research made in Punta Cana and Puerto Plata showing promising results. Here is an article in a Dominican newspaper about it.
    The article is in Spanish, but it basically says that Dr. Jose Natalio Redondo in approximately seven weeks, the experience of its health center in Puerto Plata with ivermectin has a sample of about 500 patients in an age range ranging from 20 to 96 years, excluding pregnant women and children and the prognosis seems to be promising. They began combining the action of ivermectin with hydroxychloroquine, but after a few trials found no advantages over the use of ivermectin alone.
    Now it seems they are working on a formal study based on actual clinical data.

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