i am not exactly sure what MDV and TechCm are talk
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Posted On: 04/20/2021 10:10:34 PM
Re: MD VIROLOGIST #87331
i am not exactly sure what MDV and TechCm are talking about, but if you look carefully at the PRO140 HIV papers (google scholar "lalezari PRO140) and compare the blood concentration of subcutaneous dosing to the blood concentration of intravenous dosing I think it shows that the blood concentration from intravenous dosing is at least two times higher than the blood concentration from subcutaneous dosing.
There is on article for subQ dosing and a different article for intravenous dosing.
Both article show leronlimab blood concentration vs. time over a one week period.
The blood concentration from subQ dosing is achieved around day 2 or 3.
The subQ max blood concentration is 10ug/mL at the 350mg dose.
For intravenous dose, the blood concentration at the same time is more than 20ug/mL.
Both IV and subQ plots are highly linear and show nearly identical decay time constants.
So I think those plots show that IV achieves 2x the blood concentration of subQ from the time point of peak blood concentration of subQ.
So looks like IV gets at least a 2x advantage there. A subQ 350mg dose is the same as an IV 700mg dose starting 48 hours from the dose.
And then of course, from an area-under-the-curve point of view, the IV dose is massively higher than the subQ dose during hours 0 to 48.
I find a couple of things puzzling about the reported leronlimab results to date.
First, many patients seem to respond very quickly to leronlimab. Ex-Phillippine president Estrada was extubated withing 36 hours of his subcutaneous leronlimab dose. The leronlimab had not hit peak blood concentration. It definitely takes some time for leronlimab to exit the subcutaneous compartment and get in the bloodstream. Why do some patients seem to recover so quickly, seemingly before the leronlimab even has time to take full effect?
Another puzzling thing is the Patterson RO results on the Montefiore patients. RO rises to near 100 per cent on day 14 with what looks like a simple exponential rise. Only six or seven patients worth of data and there is some scatter. It just seems to me that the RO response should have a much shorter exponential time constant characteristic.
Patterson has said many times that the quantity of CCR5 molecules expressed on the surface of t-cells can vary widely even within one individual. Maybe that is what is going on. Or maybe some other reason besides receptor occupancy is the primary driver of leronlimab critical covid efficacy.
There is on article for subQ dosing and a different article for intravenous dosing.
Both article show leronlimab blood concentration vs. time over a one week period.
The blood concentration from subQ dosing is achieved around day 2 or 3.
The subQ max blood concentration is 10ug/mL at the 350mg dose.
For intravenous dose, the blood concentration at the same time is more than 20ug/mL.
Both IV and subQ plots are highly linear and show nearly identical decay time constants.
So I think those plots show that IV achieves 2x the blood concentration of subQ from the time point of peak blood concentration of subQ.
So looks like IV gets at least a 2x advantage there. A subQ 350mg dose is the same as an IV 700mg dose starting 48 hours from the dose.
And then of course, from an area-under-the-curve point of view, the IV dose is massively higher than the subQ dose during hours 0 to 48.
I find a couple of things puzzling about the reported leronlimab results to date.
First, many patients seem to respond very quickly to leronlimab. Ex-Phillippine president Estrada was extubated withing 36 hours of his subcutaneous leronlimab dose. The leronlimab had not hit peak blood concentration. It definitely takes some time for leronlimab to exit the subcutaneous compartment and get in the bloodstream. Why do some patients seem to recover so quickly, seemingly before the leronlimab even has time to take full effect?
Another puzzling thing is the Patterson RO results on the Montefiore patients. RO rises to near 100 per cent on day 14 with what looks like a simple exponential rise. Only six or seven patients worth of data and there is some scatter. It just seems to me that the RO response should have a much shorter exponential time constant characteristic.
Patterson has said many times that the quantity of CCR5 molecules expressed on the surface of t-cells can vary widely even within one individual. Maybe that is what is going on. Or maybe some other reason besides receptor occupancy is the primary driver of leronlimab critical covid efficacy.
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