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Re: gfp927z post# 19701

Thursday, 08/07/2008 5:03:29 PM

Thursday, August 07, 2008 5:03:29 PM

Post# of 50849
GFP- I alluded to that iv vs PO slide.

If you'll allow me to continue in my role as devils advocate / party pooper:

The longer halflife in humans contributes to a more rapid rate of drug entry into the blood stream from an oral dose than would occur in rats (ie if elimination is reduced, accumulation occurs more rapidly)- of course that assumes that absorption is a constant.

Point being that in a species with a slower elimination rate (ie human), the Tmax should be quicker and so the difference between oral and iv administration may well be less.

If that is the case, you might not expect to be as big a difference in effect between iv and oral in human...

As for iv admin of CX717- well so far we have only seen a significant effect at a high (oral) dose of 2.1g and then it still is somewhere between 20-50%. Since solubility of CX717 is a limiting factor, it is unclear what kind of iv bolus would be required to get a clinically significant effect in RD. Sure, the ability to marginally increase opioid levels might be useful, but its hardly a "naloxone with analgesia maintenance"

As for imagining a wonderful CX1942, well I can imagine lots of things, but the data is what counts and that remains to be seen- even if it is more potent (IF!) and doesnt have the "artefact" (big IF!) we still dont know whether it will have some unforseen toxicity.

As for that "artefact"- it was only seen in drug treated animals, so while it was an artefact of preparation, some underlying drug-related change had occurred and its not clear what that is, or whether its a class effect.
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