Half-life measures the time it takes for half the
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Posted On: 09/14/2021 6:54:08 PM
Re: 2MartiniGi #103795
Half-life measures the time it takes for half the drug amount to still be in the plasma.
I took a look at two of the old IV trials which got me thinking. It's assumed there is a direct correlation between half-life and the effectiveness of the drug. With a receptor binding drug like leronlimab that may not necessarily be true. With 700mg and 100% occupancy of the drug there may be an excess of the drug in your system that may be eliminated from the body without ever binding. This would show a decrease in the drug amount in the plasma while having no effect on receptor occupancy. The other thing is decrease in the level of receptor occupancy would be determinate on how fast new CCR5 receptors are expressed. At half-life if only 10% more CCR5 receptors appear you'd still be at 90% occupancy.
For the brazil trials what is important is the length of time that a large percentage of the receptors are occupied and how fast the peak levels of leronlimab are in the system. In the trial that used 10mg/kg (equivalent to 700mg in a 154 lb. person) viral rebound started around 11 days. We can assume loss of receptor occupancy started occurring a few days prior. Possibly at day 7 or 8 after dosing. In IV dosing peak serum levels occur after 30-60 minutes.
If I am correct then the fast rise in serum levels means there will be no problem with 7 day dosing in the Brazil trials.
I took a look at two of the old IV trials which got me thinking. It's assumed there is a direct correlation between half-life and the effectiveness of the drug. With a receptor binding drug like leronlimab that may not necessarily be true. With 700mg and 100% occupancy of the drug there may be an excess of the drug in your system that may be eliminated from the body without ever binding. This would show a decrease in the drug amount in the plasma while having no effect on receptor occupancy. The other thing is decrease in the level of receptor occupancy would be determinate on how fast new CCR5 receptors are expressed. At half-life if only 10% more CCR5 receptors appear you'd still be at 90% occupancy.
For the brazil trials what is important is the length of time that a large percentage of the receptors are occupied and how fast the peak levels of leronlimab are in the system. In the trial that used 10mg/kg (equivalent to 700mg in a 154 lb. person) viral rebound started around 11 days. We can assume loss of receptor occupancy started occurring a few days prior. Possibly at day 7 or 8 after dosing. In IV dosing peak serum levels occur after 30-60 minutes.
If I am correct then the fast rise in serum levels means there will be no problem with 7 day dosing in the Brazil trials.
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