Thread by @Carlos_Chaccour

I have been working with #ivermectin for more than 10 years.

We need to talk about ivermectin and #COVID19

Thread 👇

#SARS_COV_2 is a positive single-stranded RNA virus

Ivermectin inhibits in vitro the replication of several positive single-stranded RNA viruses such as:
- Dengue
- Zika
- Chikungunya
- Yellow Fever

The new in vitro data from Caly et al. Show 50% inhibition of #SARS_COV_2 replication after incubating VERO cells with 2.8 uM for 2 days.

How much is 2.8 uM Carlos?

That is a good question.

sciencedirect.com/science/articl…

2.8 uM is the equivalent of a plasma concentration of 2100 ng/ml.

Lets put that into perspective.

The ivermectin dose used for river blindness is 200 mcg/kg. That is one tablet of 3 mg for every 15 kg of weight.

malariajournal.biomedcentral.com/articles/10.11…

The maximum plasma concentration reached with that dose is around 40 ng/ml.

That is 50-fold less that the concentration proven to cut viral replication in half.

There is however hope. Prove antiviral activity opens the door to carefully conducted and controlled trials.

Now, if you are considering using ivermectin on a compassionate basis you must know this:

Ivermectin can cross react with GABA-gated chlorine channels in the CNS and cause neurotoxicity. This is normally prevented by the blood bran barrier (BBB), particularly by the P-gp.

If you do not have a fully functional BBB ivermectin may not be the safe drug it usually is.

Now, hyperimflammatory states, such as the one caused by #COVID19 make the BBB leaky.

I would be careful to use ivermectin in severely ill patients with proven efficacy.

Additionally, please be careful with drug-drug interactions.

Many #COVID19 patients are receiving Lopinavir/Ritonavir.

Rito is a very good CYP3A4 inhibitor with some effect on the P-gp as well.

It can boost ivermectin increasing Cmax and potentially penetration on the CNS.

nature.com/articles/s4159…

The new direct effects on the virus reported by Caly and colleagues are very god news!

I understand the urgency. There is reason for hope!

But this required careful planning.

Some trials have already been proposed in the last few weeks.

Watch this space.

*Without* proven efficacy...

*very goOd
*this requireS

For those asking conversion
a) The molecular weight of ivermectin is 875.1 g
b) 2.8 uM = 0.0000028 Molar/L

The g/L concentration is then a x b = 0.00245 g/L which equals 2450 ng/ml

The concentrations used in the paper are then:
2.5 uM = 2187 ng/ml
and
2.8 uM = 2450 ng/ml

Addendum

Please listen to the @US_FDA

"People should never take animal drugs, as the FDA has only evaluated their safety and effectiveness in the particular animal species for which they are labeled. These animal drugs can cause serious harm in people"

fda.gov/safety/medical…

Q&A on #Ivermectin and #COVIDー19 available from @US_FDA here:

Q: Should I take ivermectin to prevent or treat COVID-19?
A: No

Q: Is there an emergency use authorization for ivermectin in the U.S. to prevent or treat coronavirus or COVID-19?
A: No

fda.gov/animal-veterin…

Here is our latest Q&A