foggynotion | 3 points | Sep 07 2020 19:15:17

Journal of Pharmaceutical Sciences: Development of a minimal physiologically-based pharmacokinetic model to simulate lung exposure in humans following oral administration of ivermectin for COVID-19 drug repurposing (US/Argentina 2020-09-04)

https://www.sciencedirect.com/science/article/pii/S0022354920304950

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[-] Z3rul | 3 points | Sep 08 2020 02:39:30

argentina is going nuts with ivermectin , there are 2 RCT trials that will be finished this month, and i hope these give the answer everyone wants. aside for that there are many other studies being done with ivermectin as prophylaxis/late use/high dose usage and effective and safe dosage for covid19

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[-] luisvel | 1 points | Sep 09 2020 15:56:52

Would you please add links to the trials data showing end dates? Thanks!!

Edit: found the IVERCAR trial. Looks like it was “returned after quality control review” the 27th. I am not sure if this is common or if there is a risk the trial had a major flaw.

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[-] Z3rul | 2 points | Sep 11 2020 02:35:06

Tandil - Centro de Investigación Veterinaria Tandil CIVETAN

Ivermectin Effect on SARS-CoV-2 Replication in Patients With COVID-19

 

https://www.youtube.com/watch?v=aycAFTDVL3M

Dr. Carlos Lanusse gives an update on the study, and says partial results can be expected by the end of september.

 

Corrientes - Instituto de Cardiología de Corrientes

Ivermectin to Prevent Hospitalizations in COVID-19

 

https://www.youtube.com/watch?v=hegIk1EkUBQ

They talk about reducing the N of subjects to get early results

 

The IVERCAR protocol , follow up measures for both groups aren't well detailed and explained

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[-] luisvel | 1 points | Sep 11 2020 03:10:47

Excelente. Gracias!!

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[-] foggynotion | 2 points | Sep 07 2020 19:30:24

This was accepted 2020-08-31 but published Sept. 4th

Full Text PDF

This study shows that ivermectin inhalers or cleaning sprays could be very effective:

Our simulated peak lung concentration of 772 ng/mL following a single oral 120 mg dose is well below the reported in vitro IC50 of 1750 ng/mL as seen by other groups. (..Monash Study) [11, 18, 19] The mPBPK model allows the simulation of different formulations (e.g., an ethanol-containing solution shown to have approximately twice the systemic availability of ivermectin tablets) as well as the effect of high fat meals to increase lung exposure to ivermectin. Reformulation of ivermectin to an inhaled therapy may increase drug exposure in the lungs while minimizing the potential toxicities associated with high plasma concentrations that have not been established as safe. Ivermectin is a compelling candidate for consideration as part of a combination regimen by making the host cell environment unfavorable for SARS-CoV-2 assembly and replication after IMPα/β1 heterodimer dissociation and inhibition. Ivermectin is also lipophilic with a pKa 8, which has been shown to be beneficial for uptake into the lungs from plasma (Figure 3). We hypothesize that ivermectin in combination with other agents of differing antiviral mechanisms of action could be efficacious and/or reduce the ivermectin exposure necessary to eradicate SARS-CoV-2 through synergistic effects.

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[-] wallahmaybee | 1 points | Sep 08 2020 16:50:10

So could one turn cattle ivermectin pour-on into a nasal spray if docs are too scared to prescribe?

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[-] TrumpLyftAlles | 1 points | Oct 29 2020 17:24:35

Interesting idea. I think that would be a cheap solution (no pun intended).

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[-] TrumpLyftAlles | 1 points | Oct 29 2020 17:23:30

Abstract
SARS-CoV-2 utilizes the IMPα/β1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor. Ivermectin has shown antiviral activity by inhibiting the formation of the importin-α (IMPα) and IMPβ1 subunits as well as dissociating the IMPα/β1 heterodimer and has in vitro efficacy against SARS-CoV-2. Plasma and lung ivermectin concentrations vs. time profiles in cattle were used to determine the apparent plasma to lung tissue partition coefficient of ivermectin. This coefficient, together with a simulated geometric mean plasma profile of ivermectin from a published population pharmacokinetic model, was utilized to develop a minimal physiologically-based pharmacokinetic (mPBPK) model. The mPBPK model accurately described the simulated ivermectin plasma concentration profile in humans. The mPBPK model was also used to simulate human lung exposure to ivermectin after 12, 30, and 120 mg oral doses. The simulated ivermectin lung exposures reached a maximum concentration of 772 ng/mL, far less than the estimated 1750 ng/mL IC50 reported for ivermectin against SARS-CoV-2 in vitro. Further studies of ivermectin either reformulated for inhaled delivery or in combination with other antivirals with differing mechanisms of action is needed to assess its therapeutic potential.

Almost halfway to the Monash 48 hours result, which the co-author Dr. Wagstaff says will be shown to be higher than necessary in her current dosing study that is using human cells instead of vero (green monkey) cells that Monash 48 hours used.

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[-] foggynotion | 2 points | Oct 29 2020 19:16:00

Didn't realize they used monkey cells in the monash study, I'd definitely imagine the ivermectin would be more effective in vivo with human cells

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[-] TrumpLyftAlles | 1 points | Oct 29 2020 19:18:46

I missed it too. A scientist protesting the CONCENTRATION TOO HIGH!!! pointed it out in a letter to some publication. He said that the vero cells do not express ACE2, period, which makes them a terrible basis for covid-19 research. Remember, Monash 48 hours was published on April 3, 2020 so relatively little was known as they did their research. I communicated briefly with Dr. Wagstaff (Monash co-author) about it and she said that vero does express ACE2, but at a much lower level than human cells.

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