Even IF some of the drugs work, chances are you still won't get them.

[mpreorder]

I've been a clinical pharmacist in a hospital for over 30 years. I've seen shortage after shortage of COMMON drugs. Our buyers have to scramble to get them more often than anyone who's ever been in a hospital would be comfortable with. As a last resort we go to the "grey market". These are companies that somehow manage to have a supply, and guess what folks...capitalism at it's finest is at work and 400% or more increases in cost are not uncommon. But I digress.

The real reason you won't get the drugs is because there simply isn't enough out there. Did anyone else read how a manufacturer had 3 million doses of chloroquine available? Or 10 million doses of hydroxychloroquine? The population of the US is >310 million....at a 40% infection rate (low estimate) that's over 120 million people infected. True, not all will need the drug, so lets say they reserve it for the sickest. Right now these is one estimate that about 12% of those infected require hospitalization, so lets say this is the population that needs the drug(s) (This number varies depending on age, co-morbidities, etc.) So something over 14 million people will need treatment. OUR SUPPLY IS SIMPLY NOT ENOUGH!!

What about other manufacturers or making more? Good questions. In my 30+ years I don't think I've ever seen chloroquine used, but hydroxychloroquine is used for people with rheumatoid arthritis. We usually have 1 or 2 patients in our hospital on it at any one time. Read that as being that it's just not that commonly used, even for the indication it's intended for. I can't speak to what other manufacturers have on hand, but can tell you that as of yesterday our hospital was not able to get any. (We have enough to treat about 100 patients). I also can't speak about manufacturing capability, especially during a pandemic where supply lines are wavering. Hopefully they can ramp up production in a meaningful way.

I know I sound like the sky is falling, but it almost is. We have a central government that doesn't give a rats ass about it's people and worse, are getting in the way of those that do. I'm looking to move out of my house because my wife has MS and I can't chance giving to to her. The leadership in my hospital, while communicating daily, isn't saying much in the way of anything concrete, no less what we are going to do when the staff starts getting sick. I work in a Coumadin clinic where over 90% of our patients are over 70. We're going to see many of them die from this.

OK, that last paragraph was a rant, forgive me. I know it seems like I'm new here but I've actually been on DU since the Bush years. You guys are kindred spirits to me and I truly wish you all the best.

[Phoenix61]

1. My mom was in the hospital and the doc

ordered IV Tylenol. Time went by and nothing was happening. Took hours for them to admit they didn’t have any. I hate to think what would have happened if I hadn’t been there.

[magicarpet]

2. Thank you for posting,..

... and sharing your viewpoints and perspectives. The best to you and yours as we all negotiate the maze.

[lostnfound]

3. If available quickly and broadly -could reduce transmission and address hospital capacity

The Japanese drug favipiravir / Avigen causes viral count to drop enough to get to negative test in a median of 4 days instead of a median of 11 days, tested across 340 patients.

Seems to me that it could keep people out of hospital if given early, and reduce transmission.

[MineralMan]

5. The question about favipiravir is how long it would take to

ramp up production of it, really. They're testing it, and have been for a few years, in several situations. However, I doubt they have a full-scale production facility ready to make enough of it for the current situation, really. Manufacturers of that class of antivirals could probably make this new one, if they had a license from fujifilm to do so. But the economics all around might make that difficult or impossible.

It might well be the best possible choice of an antiviral, but I suspect we're a long time away from having adequate supplies of it for widespread treatment.

[Igel]

6. I'm not going to make you happy with this.

Looking at remdesivir and its synthesis I see slowness and bottlenecks everywhere. From wiki's remdesivir page.

Some of the reagents aren't going to be in high demand. I don't see "speedy" oozing from the process. And I see no mention of yields, which I suspect are low for most of the steps. And I don't see why favipiravir would necessarily have a much simpler synthesis. (Makes me appreciate all the work done to edit yeast genomes to produce this kind of thing.)

Synthesis of Remdesivir in structural formula.
Remdesivir can be synthesized in multiple steps from ribose derivatives. The figure below is one of the synthesis route of remdesivir invented by Chun and coauthors from Gilead Sciences.[29] In this method, intermediate a is firstly prepared from L-alanine and phenyl phosphorodichloridate in presence of triethylamine and dichloromethane; triple benzyl-protected ribose is oxidized by dimethyl sulfoxide with acetic anhydride and give the lactone intermediate b; pyrrolo[2,1-f][1,2,4]triazin-4-amine is brominated, and the amine group is protected by excess trimethylsilyl chloride. n-Butyllithium undergoes a halogen-lithium exchange reaction with the bromide at −78 °C (−108 °F) to yield the intermediate c. The intermediate b is then added to a solution containing intermediate c dropwise. After quenching the reaction in a weakly acidic aqueous solution, a mixture of 1: 1 anomers was obtained. It was then reacted with an excess of trimethylsilyl cyanide in dichloromethane at −78 °C (−108 °F) for 10 minutes. Trimethylsilyl triflate was added and reacts for an additional 1 hour, and the mixture was quenched in an aqueous sodium hydrogen carbonate. A nitrile intermediate was obtained. The protective group, benzyl, was then removed with boron trichloride in dichloromethane at −20 °C (−4 °F). The excess of boron trichloride was quenched in a mixture of potassium carbonate and methanol. A benzyl-free intermediate was obtained. The isomers were then separated via reversed-phase HPLC. The optically pure compound and intermediate a are reacted with trimethyl phosphate and methylimidazole to obtain a diastereomer mixture of remdesivir. In the end, optically pure remdesivir can be obtained through chiral resolution methods.

[MineralMan]

7. Thanks. I thought as much.

I'm not an organic chemist, so that description isn't completely transparent for me, although I can understand the complexity of the synthesis.

I'm sure that most people have no idea whatsoever of how such drugs are made. I'm absolutely certain that people like Trump can't even imagine the process at any level.

So, I'm sure you're right and a mass production-level process is a long way out. Nobody's going to design such a production system without more evidence of efficacy and safety. So, we're not going to see massive numbers of doses available in any reasonable time.

Apparently the developer of favipiravir is FujiFilm. From what I read, they have been doing trials of it for various things since 2014. It sounds like an antiviral looking for a disease, really. The early trials against COVID-19 seem promising, but still not promising enough to design a production line for the drug.

Sadly, the more common antivirals haven't tested out well against this virus. I'm sure they're still testing combinations to see if they can get some good activity going. None of those things, though, are going to be of use in the immediate crisis.

I appreciate your looking this stuff up!

[lostnfound]

8. I agree. Also may have teratogenic effects. But epidemiology Vs individual outcomes...

Reading the comments about it, some of them said “it didn’t help the people with the worst cases”. Also they’ll say one of these drugs won’t cure it, or won’t prevent it.

Seems to me if you could produce enough to treat the positives, and cut down the median virulent phase from 11 days to 4 days, you’ve accomplished a lot at slowing the spread. At flattening the curve. And maybe many severe cases will be averted because the replication of the virus will be interrupted — thus reducing the strain on the healthcare system.

[eyeofnewt]

4. The clinical trial

For hydroxychloroquine is just now accepting patients at the Univ of Minnesota. It’s not a proven therapy yet, and I’m sure we all hope it will be. Donations by Teva and Bayer sound good, but it’s not enough- and ramping up production by Mylan does too. But even off patent, they intend to profit- it will become a cash cow like insulin. Let’s face it, compassion isn’t even remotely in play. And if it doesn’t work? Will the manufacturer then want a bail-out for their “patriotic” endeavor? Then we’re back to the same old circular pattern- who gets it, insured? Availability to uninsured? Leads to the whole insurance debate of private vs for-all and Big Pharma and their price gouging ways. This alone will generate enough hearings in DC to keep anyone from getting it.

Sorry to hear you may have to be separated from your wife during this; I’m staying completely away from the person I’m closest too also-my fear of him not surviving is almost all consuming. Good luck and take care, mpreorder.

[Wounded Bear]

10. Gov Cuomo said they are starting one in NYS, didn't hear which clinic/college...nt

[Wounded Bear]

9. That's because we don't have a healthcare system...

we have a for profit healthcare industry.

Common drugs are not profitable, not as much as sexier miracle drugs that solve problems most people have never heard of, but can be scared into begging their doctors for because of some TV ad. Common drugs, as you refer to them, should have mandatory minimum quantities manufactured and available as determined by scientific studies of need based on statistics. There should never be shortages of them.

If ever there was an industry that needs strict government regulation and governance, it is our healthcare industry. Nothing 'systematic' about it.