Hi board. Been researching z160 and understand that they were able to increase the cmax by 5 times over the old formulation. My question is whether anyone knows if this is blood concentration or csf concentration (corticospinal fluid - the stiff the brain and spinal cot are bathed in). It matters. Increasing the plasma concentration does not necessarily increase the csf concentration. We know that the previous formulation did cross the blood brain barrier to some extent as evidenced by the fact that there was some improvement in pain. And we can assume that increasing the plasma concentration should increase the concentration in the csf. But it would help if we knew from phase 1 if the increase in concentration was actually an increase at the receptors. Anyone?
Jim's blood pressure is up again with your question kdalglish, but its all good:
"Drug entry into CSF is not a measure of BBB permeability
Drug entry into the CSF compartment from blood should not be taken as an index of drug transport across the BBB. Drug transfer from blood to CSF occurs across the choroid plexus, which is leaky compared to the BBB. Virtually all small and large molecules in blood penetrate into CSF, at a rate inversely related to the molecular weight of the substance. The finding of drug entry into CSF is expected, and does not discriminate between those drugs that do, and do not, cross the BBB. This is because the choroid plexus, which regulates drug transfer into CSF from blood, and the brain capillary endothelium, which regulates drug transfer into ISF from blood, are comprised of completely different epithelial/endothelial barriers. The application of recent proteomics technology will enable the description of the different transporter expression profiles in the BBB and choroid plexus . The difference between drug transfer across the choroid plexus and across the BBB is illustrated in the case of azidothymidine (AZT). This drug is rapidly transported across the choroid plexus epithelium and rapidly enters the CSF compartment in humans . However, there is negligible transport of AZT across the BBB in vivo, owing to active efflux transport processes at the brain microvasculature ."
Google for the reference, Ciao!
Sentiment: Strong Buy
From the last investment conference transcript we're talking about blood concentrations--
"This gets us to the blood levels we believe are going to be necessary for efficacy. Again these are allometrically scaled; we're taking from the animal about what we think we're going to need in humans."
Sentiment: Strong Buy
kda: It seems to me that anyone looking in from the outside without the intimate knowledge of the science involved can't really add anything to the equation by knowing the answer to this one. The speculation involved in trying to second guess the program is not beneficial to actually improving the understanding of the program. Rather it can only provide a base for building false credibility, of the poster, that will be used for negative posts at a later time.
Normally I let you clowns shoot yourselves in the feet before calling you out but I'm fed up with this crud. Go back to the cave and try to figure out a better shtick.
Jim Long and calm
Sentiment: Strong Buy
Jim, based on his posting history on other boards and the fact that he's been a yahoo member for five years, I think you're probably wrong about his motives. I think he legitimately wants to know the answer to his question. Just my opinion.
Are you always a prik or only when the question being asked is beyond your understanding? I happen to be long many thousands of shares here and hoping to make a lot of money. I am enamored by the mechanism of action of Z160 and in fact could see great benefit from it in my particular field of medicine. It turns out that I understand the science quite well. I knew this was taking a shortcut asking the board when I can do more DD myself , but I thought it was worth a try.
I am not trying to second guess "the program" as you call it. I just wanted to know if anyone here, including the clown this is in reply to, had heard in any venue a similar question asked. It is obvious that there is anecdotal evidence supporting CSF levels of the previous incantation of the drug, but although it is likely, we cannot automatically assume that increasing plasma concentration necessarily increases central nervous system exposure. It seems like an appropriate question and one that has likely been asked somewhere, sometime of the company.
I will take my question directly to management.
And Jim comes out swinging with the hay maker..... one, two, three, four, five, six, seven, eight, nine, ten.. and it's all folks, have a safe drive home and don't forget to buy a t-shirt at the door.
I am almost certain it is blood concentration. The Cmax has an 8 fold increase and the Area Under the Curve has the 5 fold increase. That's why the AUC is important: The longer it remains in the blood, the more molecules pass thru the blood-brain membrane.