Route of administration reported so far for EINDs
Post# of 154001
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Posted On: 08/09/2020 7:43:41 PM
Re: MD VIROLOGIST #48006
Route of administration reported so far for EINDs and expanded access trials is IV. It appears the half-life of VIP is VERY short, less than 2 minutes, and that would explain why it is infused over 12 hours for 3 consecutive days at ascending doses. That route of administration is hardly simple.
Case report - discusses route of administration (12 hour IV)
https://www.preprints.org/manuscript/202007.0178/v1
Half-life and other PK:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412244/
Effects of VIP on heart:
https://academic.oup.com/cardiovascres/articl.../27/293330
The second trial for which they just got approval is for inhaled formulation, and that is simpler. One wonders how long it would act with 3 puffs a day.
Synthetic VIP is not a viral entry inhibitor. The Brazilian pre-print describing invitro human lung cell data said the MOA is unknown.
https://www.biorxiv.org/content/10.1101/2020....806v2.full
My hunch is that VIP acts by increasing surfactant production. This immediately helps breathing, and second, some of the surfactant proteins, SP-A and SP-D, appear to have direct anti-viral and immunomodulatory activity.
https://www.sciencedirect.com/science/article...8110003293
https://www.atsjournals.org/doi/10.1513/Annal...1411-507FR
https://www.atsjournals.org/doi/full/10.1513/...0701-018AW
The Brazilian pre-print also was pretty weak data,with only ~40% inhibition at the lowest dose (compared to others with direct antiviral suppression of over 95%), and even less at higher doses. How does one explain this "backward" / inverted dose-response curve?
The novel thing about Brazilian study versus other in vitro SARS2 work is that they studied healthy control monocyte cultures too, to see the effects on cytokine production. It would be interesting to see what leronlimab would show in such an experiment.
Case report - discusses route of administration (12 hour IV)
https://www.preprints.org/manuscript/202007.0178/v1
Half-life and other PK:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412244/
Effects of VIP on heart:
https://academic.oup.com/cardiovascres/articl.../27/293330
The second trial for which they just got approval is for inhaled formulation, and that is simpler. One wonders how long it would act with 3 puffs a day.
Synthetic VIP is not a viral entry inhibitor. The Brazilian pre-print describing invitro human lung cell data said the MOA is unknown.
https://www.biorxiv.org/content/10.1101/2020....806v2.full
My hunch is that VIP acts by increasing surfactant production. This immediately helps breathing, and second, some of the surfactant proteins, SP-A and SP-D, appear to have direct anti-viral and immunomodulatory activity.
https://www.sciencedirect.com/science/article...8110003293
https://www.atsjournals.org/doi/10.1513/Annal...1411-507FR
https://www.atsjournals.org/doi/full/10.1513/...0701-018AW
The Brazilian pre-print also was pretty weak data,with only ~40% inhibition at the lowest dose (compared to others with direct antiviral suppression of over 95%), and even less at higher doses. How does one explain this "backward" / inverted dose-response curve?
The novel thing about Brazilian study versus other in vitro SARS2 work is that they studied healthy control monocyte cultures too, to see the effects on cytokine production. It would be interesting to see what leronlimab would show in such an experiment.
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