I will never understand the Ivermectin craze.
Ivermectin cannot work as an antiviral. Pharmacologically it doesn't make sense and hasn't from the very beginning. Let me explain:
Ivermectin's potential use for COVID-19 began when a group showed that
IN TISSUE CULTURE (not even an animal study) SARS-COV-2 viral replication was inhibited 50% at a dose of 2 uM.
On the surface, sounds great. We should pursue it. Here are the issues --
The 2 uM concentration is
35x HIGHER than the maximum plasma concentration your body would have after oral administration of the approved dose of ivermectin. Even if you took 10X the approved oral dose, you STILL would not reach the 2 uM concentration the original study used. The amount that you have in your body after taking Ivermection orally is 0.0873 uM, not even close to the original 2 uM used.
Quote:
Caly et al.1 reported that ivermectin inhibited severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in vitro for up to 48 hours using ivermectin at 5 M. The concentration resulting in 50% inhibition (IC50 ; 2 M) was > 35 higher than the maximum plasma concentration (Cmax ) after oral administration of the approved dose of ivermectin when given fasted. 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 g/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. Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations do not reach the IC50 , even for a dose level 10 higher than the approved dose. Even with the high lung:plasma ratio, ivermectin is unlikely to reach the IC50 in the lungs after single oral administration of the approved dose (predicted lung: 0.0873 M) or at doses 10 higher that the approved dose administered orally (predicted lung: 0.820 M). In summary, the likelihood of a successful clinical trial using the approved dose of ivermectin is low. Combination therapy should be evaluated in vitro. Repurposing drugs for use in coronavirus disease 2019 (COVID-19) treatment is an ideal strategy but is only feasible when product safety has been established and experiments of repurposed drugs are conducted at clinically relevant concentrations.
https://pubmed.ncbi.nlm.nih.gov/32378737/To top it off, in Virology when we are trying to discover new antivirals, we use IC90 as a standard. This equates to 10-fold reduction in amount of viral particles. The original study didn't even use IC90, but instead IC50 (50% reduction). On the surface 50% might seem large, but not when you are dealing with numbers on a log scale like the millions of viral particles your body produces during viral infection.
The IC90 is usually 10X the IC50 -- this is true for most inhibitors. To get to the IC90 for ivermectin using the data the original study found, you would come out to 20 uM final concentration of the drug needed in your lungs to show an effect. Again, that is
250X the normal dose administered orally.
It has never made sense as a real therapy, and why many ignored the data when it came out. This wasn't a cover-up or 'Big Pharma' ignoring the cheap therapeutic they couldn't profit from. It simply doesn't work.
If anyone is saying they've seen ivermectin work, its the placebo effect playing out without a large enough sample size.
