TehCaster | 12 points
Celebrating one year since the Monash in vitro studyAnd we still don't have definite results of a large trial. Vaccines were developed and massively used in less than a year, sigh.
https://www.sciencedirect.com/science/article/pii/S0166354220302011
Received 18 March 2020, Revised 27 March 2020, Accepted 29 March 2020, Available online 3 April 2020.
At least the "100 times normal dose would be needed to achieve this in vivo" argument was not part of the latest WHO guidelines rationale, after it was repatedly mentioned by NIH, FDA, EMA... a small victory?
Anyway, in case it cames back somewhere, in the "birthday" spirit I checked what we know on this topic, feel free to add:
One of the initial objections from Chaccour: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253113/
But he mentions "However, some in vivo effect may be possible even if efficacious in vitro concentrations are physiologically unattainable." and "However, evidence from animal models showing up to 3-fold higher levels in pulmonary tissue than in plasma 1 week after oral dosing leaves the door open for further research, in particular for the treatment of respiratory viruses"
And later in his blog post: https://www.isglobal.org/en/healthisglobal/-/custom-blog-portlet/questions-and-answers-about-ivermectin-and-covid-19/2877257/0
There he says "60-fold higher than the maximum concentration after usual doses" and
There is equipoise —this is a term used in bioethics to define a situation in which there is reasonable doubt of whether a drug might be of use or not
Notice, reasonable doubt, not a "this cannot work and we will ignore it because..."
COVID-19 is a public health emergency of international concern and there is no specific treatment for it. This fact, together with the excellent safety profile of ivermectin combine to warrant research on its potential use. Additionally, extrapolating directly from a Petri dish into a live organism is not correct. Several factors may contribute to make ivermectin efficacious in vivo at lower doses than those described by Caly et al, here are some of them
And lists a number of factors, some we know also from Dr. Marik's talks (immune system, higher penetration in lungs vs monkey kidney cells, more potential mechanisms that cannot be in action in a cell culture).
He even links to PK model study that suggests IVM could actually achieve 10x the needed concentration, not 100x less, if I understand that properly: https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.1909 (although I didn't find the assumed dose for IVM there?)
And Dr. Wagstaff herself supposedly has repeated the study on human lung cells. Here https://www.smh.com.au/national/how-an-australian-covid-cure-conquered-the-world-despite-no-robust-evidence-it-works-20201106-p56c7m.html there is:
To get to the levels in Dr Wagstaff's initial study, a person would need to take a dose 10 to 30 times higher than ever studied in humans, Professor Sullivan says.
Dr Wagstaff rejects this, and says she has unpublished data showing "the drug works at lower concentrations which are definitely achievable based on all published modelling".
Dr. Marik/Dr. Kory said repeatedly also that they have this unpublished data from Dr. Wagstaff, mention them on their slides, and this guy (who seems to know what he's doing) recalculated that the concentrations should be achievable (despite some errors that Kory supposedly did) https://twitter.com/__ice9/status/1352460130013630464