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Potentially its problematic part of the next set of studies was...

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suhm

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15/06/18

08:45

Post #: 33726418
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Originally posted by Librium ↑

My concern regarding the dose is indeed speculation, but it is not without evidence. Read the very interesting research paper that was published in the British Journal of pharmacology provided on the ACW website and you will come to the following:

Pharmacokinetics
In the single ascending dose study UE2343 reached a maximum
plasma concentration (Cmax) within 3.5–4 h following
administration of 10, 18, 25 and 35 mg of UE2343 (Figure 2).
Plasma levels of UE2343 at doses of 2 and 5 mg were below
the level of quantification, and data are not reported.

The current study is using a once per day 10mg dose
Note that the 5mg dose failed to even reach detectable levels in plasma. Note in the chart how quickly plasma concentrations fall after peaking about four hours after a dose.
I assume that explains this last sentence in the paper before the acknowledgments.

The data described
herein suggest that the requisite level of 11β-HSD1 inhibition
in brain is achievable over a prolonged period following
twice-daily oral administration of UE2343.

The dosing used in the current study does seem to be the most conservative dose possible that could still theoretically have a treatment effect.
We are after all still unsure of the safety of this compound and the last thing anybody wants is to cause harm.

This paper also attempts to explain the failure of ABT-384. For those that have not DTOR this was a drug tested in a phase 2 trial that failed to show efficacy. Same target as Xanamem. Abbott Pharmaceuticals.
Apparently despite Abbott believing that ABT-384 was " tested at doses associated with complete brain HSD-1 inhibition" the reality was that the CSF concentration was too low for adequate inhibition. If I have time over the weekend I will read the ABT - 384 paper as I am interested in whether there was any trend in efficacy.

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Potentially its problematic part of the next set of studies was to actually quantify the inhibition.

https://actinogen.com.au/wp-content/uploads/2017/06/20160310-Investor-Presentation.pdf

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