I read Lasar's article, and while I am personally a Lasar fan and enjoyed the write-up, I would like to put Z944 aside for the moment.
I think we all know why we are here. We are here for Z160, the Neuromed redux.
Question. Is 6X increased bioavailability enough, and is bioavailability the only concern that we face? Does anyone have half-life data? How long does this molecule stay in the body regardless of bioavailability. Corrigan should have mentioned this. Maybe I missed it.
This is a basic pharmacokinetics question. If the effects are extremely short-lived, we could have a problem. If Z160 is degraded rapidly in the body/liver, it may not be effective.
Merck may have left for two reasons, bioavailability and pharmacokinetics. Did anyone hear Corrigan mention anything about this? I suppose this could be partially resolved by dose and frequency, but how hard is it to reach an effective dose, and is this why bioavailability was an issue in the first place. The two could be connected.
Anyway, if anyone knows, it would be nice to hear the facts about this.
For a "Scientist" this answer should be quite obvious. Both ongoing z160 phase 2 trials dosages are 375mg BID. BID means taken orally twice a day. Therefore, it is logical that each dose stays in the body approximately 12 hours. Of course it is more complicated than this because at 12 hours the concentration is likely less than half of the maximum level which likely hit around hours 3-4. The concentration will taper off from this high to a point(Hopefully after 12 hours) where therapeutic relief is no longer gained. Hopefully, at this point, another pill has already been ingested and has begun entering the bloodstream.
Rest assured this bioavailability was already established in the first phase 2a trials. We are on phase 2b!!!!!
Many thanks. I wonder if the toxicology data prevened them from going to 3 times per day? Chronic neuropathic pain may take higher initial doses. As I recall, Z160 was in Merck's hands for a while. I am not entirely convinced that bioavailability alone was the only issue because they probably just increased the dose in their animal models. But, if the dose given does block the calcium channels in saturated fashion at 3-4 hours and more is in fact not needed, the pain level should be reduced. Reduced, but perhaps not entirely eliminated unless you believe that the N-type calcium channels are the only pain signaling route. Reduced by how much is the next question, and is it enough? We are not talking about global perception of pain here, we are talking about a very specific target. A person with chronic pain might be better off moving to Colorado and lighting up.
Great one paddler. Lasarboy is relentless in using his aliases to cast doubt on things.
Anyway, I think all of these questions were answered in the single and multiple dose studies in phase 1. Without the bioavailability, concentration and duration in the body they would really be going into a dark cave for phase 2. Asking these questions now is just stupid IMO.