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Posted On: 02/25/2021 11:51:15 PM
Post# of 148899
yes that graph is the LL blood concentration after a 700mg intravenous infusion.
at the end of the intravenous infusion, LL concentration is around 200ug/mL, and then decays with an exponential decay constant of around one day or maybe its two it can be calculated from the slope of the graph.
also in that same article is a plot of receptor occupancy circa 2010.
receptor occupancy graph shows that on either day 2 or day 3 there is a reduction in lymphocytes with "unoccupied CCR5" of probably at least 90%. probably this measurement of receptor occupancy in 2010 is nothing like what Patterson does so perhaps meaningless.
(i would just post the graphs from the lalezari papers but LOL i can't figure out how to do it. TechGuru posted an instruction set. But it had 13 steps. I am no good at statistics but I know my probablity of success with 13 steps is low
Then I watched a youtube video after searching "how to post photos on investorshangout". Settings>>>MyPhotos and then copy, open post and paste. Seemed easy. Copy worked just like in the vid but paste has the popup menu but nothing happened. this website is just flaky)
the LL blood concentration from the subQ HIV dosing (google scholar "lalezari pro140" brings it right up) shows a peak LL concentration of 10 micrograms per milliliter at 324mg dose, its linear so 700mg subQ probably hits 20 micrograms per milliliter no problem.
the subQ peack dose does not happen until 48 hours after the subQ injection.
Clearly the intravenous hits a higher blood concentration far more quickly than the subQ.
So much so that you have to wonder why they didn't do IV for covid but lack of enough IV patients probably didn't meet the safety gate.
One question I have is why does it take two weeks to achieve 100% RO in the Patterson results?
At day 8 the LL concentration is going down, but somehow between day 8 and day 14 the RO occupancy rises from 80% to 100%. How is that possible?
And I wonder in the subQ case for covid, how does the RO level not hit 100% in a day or two?
Is the binding equation for LL to CCR5 a highly asymmetric function where the exponential time constant to hit the CCR5 target is one to two days and the dwell time on-target once the target after the hit is one week? does any molecule even work like that?
modelling of LL concentration in blood is pretty easy. simple first order differential equation. and easy to measure in the patients.
the LL concentration in blood should provide some insight into the mechanism or mechamisms of action for LL.
at the end of the intravenous infusion, LL concentration is around 200ug/mL, and then decays with an exponential decay constant of around one day or maybe its two it can be calculated from the slope of the graph.
also in that same article is a plot of receptor occupancy circa 2010.
receptor occupancy graph shows that on either day 2 or day 3 there is a reduction in lymphocytes with "unoccupied CCR5" of probably at least 90%. probably this measurement of receptor occupancy in 2010 is nothing like what Patterson does so perhaps meaningless.
(i would just post the graphs from the lalezari papers but LOL i can't figure out how to do it. TechGuru posted an instruction set. But it had 13 steps. I am no good at statistics but I know my probablity of success with 13 steps is low
Then I watched a youtube video after searching "how to post photos on investorshangout". Settings>>>MyPhotos and then copy, open post and paste. Seemed easy. Copy worked just like in the vid but paste has the popup menu but nothing happened. this website is just flaky) the LL blood concentration from the subQ HIV dosing (google scholar "lalezari pro140" brings it right up) shows a peak LL concentration of 10 micrograms per milliliter at 324mg dose, its linear so 700mg subQ probably hits 20 micrograms per milliliter no problem.
the subQ peack dose does not happen until 48 hours after the subQ injection.
Clearly the intravenous hits a higher blood concentration far more quickly than the subQ.
So much so that you have to wonder why they didn't do IV for covid but lack of enough IV patients probably didn't meet the safety gate.
One question I have is why does it take two weeks to achieve 100% RO in the Patterson results?
At day 8 the LL concentration is going down, but somehow between day 8 and day 14 the RO occupancy rises from 80% to 100%. How is that possible?
And I wonder in the subQ case for covid, how does the RO level not hit 100% in a day or two?
Is the binding equation for LL to CCR5 a highly asymmetric function where the exponential time constant to hit the CCR5 target is one to two days and the dwell time on-target once the target after the hit is one week? does any molecule even work like that?
modelling of LL concentration in blood is pretty easy. simple first order differential equation. and easy to measure in the patients.
the LL concentration in blood should provide some insight into the mechanism or mechamisms of action for LL.
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