Rapamycin bioavailability webinar (generic vs compounded)

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#1

Dear Community,

You are cordially invited to a webinar hosted by AgelessRx on our upcoming paper presenting the results of bioavailability data of rapamycin comparing commercially available generic with compounded tablets.

Time/Date: Friday, August 16 2024 at 3pm ET
Location: Launch Meeting - Zoom

Topics being covered:

  • background on the study (why we needed to do this study)
  • results of the study
  • the practical implications of the study
  • a mini-review of rapamycin in the lens of sirolimus levels

The webinar will be recorded and available on the AgelessRx YouTube channel shortly after for those who can’t make it.
Bring your questions and your thinking caps!

Regards
Sajad Zalzala, MD

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#2

If you have any questions you would like answered, please post them here and we will queue them up and do our best to make sure we have time to address them!

Best

Girish Harinath
Senior Research Manager
Applied Science, AgelessRx

4 Likes
#3

Here are some questions

  1. Should we try to strive for some kind of standardized way of sharing dose regime because bioavailability differs between generic and compounded Rapamycin? For example “generic 6mg/weekly”. This to avoid confusion.

  2. What is the next step after this? Will you do deeper work around this in the clinic?

  3. Curious to know what is the latest status of the PEARL trial? When will that data be published?

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#4

I think I rather know what is the optimum level of rapamycin to have in our system after 12 hours and 36 hours. Easier to work backwards :wink:

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#5

Is Everolimus a better mTOR inhibitor than Rapamycin?

  • Everolimus has shorter half-life, which means fewer side effects and shorter rest periods ?

  • Everolimus inhibit mTORC2 more or less? (Inhibit MTORC2 is usually considered harmful)

  • Everolimus has better oral bioavailability(20%) than Rapamycin(14%) ?

  • Everolimus is easier to cross BBB(brain blood barrier) than Rapamycin, which means better effects on the aging brain ?

  • 10mg Everolimus equal to 6mg Rapamycin ?

  • 20mg/week Everolimus is reasonable?

  • Which indian manufacturer of Everolimus is the best quality? Glenmark?

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#6

Hard to say if it’s better as much less researched, but possibly. Best brands probably zydus and glenmark. See this thread Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?

I recently purchased a bunch of Glenmark Everolimus thinking that it might be much more package efficient (given the 10mg tablets), but the packaging on these is quite large, taking must as much space as probably 10X1mg rapamycin tablets.

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#7

Everolimus is easier to cross BBB(brain blood barrier) than Rapamycin, which means better effects on the aging brain ?

Curious question, where have you found the data that Everolimus crosses the BBB easier than Rapamycin? Do you have any study to refer to?

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#8

Now that is going into uncharted territory. Way off my comfort zone. I’m happy to stick to regular rapamycin for now.

#9

The paper just went live on the preprint server

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#10

@Krister_Kauppi

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#11

Here is a link to the webinar on Youtube where Sajad Zalzala, Girish Harinath and Stefanie Morgan from AgelessRx go through the Rapamycin bioavailability study.

And here is the study.

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#12

A question that is controversial and perhaps a bit off topic but on everyone’s mind…

Is Rapa AUC or peak more important for longevity and immune function impact of Rapa? IE, should a person aim for a high peak (bbb?) but a short residence time (clear quickly) to reduce side effects…via taking a higher dose of Rapa on empty stomach, for example?

Or should a person aim for slow absorption and long residence time even at the cost of lower peak rapa in blood, possibly by taking a lower dose of rapa (perhaps two doses in short sequence) with a fatty meal?

1 Like
#13

Adam Salmon’s response to this question:

Speaker 2 12:24
Okay, do you have any sense on longevity purposes, whether it’s AUC?, CMax?, what do you think are key factors in in the effectiveness of rapamycin?

Speaker 1 12:36
So, you know, you you raise this point, I’ll have to come back to the mouse, because we don’t know. My general feeling is it’s probably something like the AUC and this is based on the fact that, you know, despite what some people might say, the chronic rapamycin treatment has still been the most consistent effect. And the one test that really go did it same time. Test different ways to do it, by the ITP every day in the diet, still did the best.

Source: Adam Salmon's Marmoset Longevity Study - #4 by RapAdmin

1 Like
#14

Yes, I saw that before; good interview. I’m still gathering data (opinions) before I adjust my methods. It’s nice to get multiple points of view. I already know that there isn’t a clear answer, but I’ll go with the dominant leaning among the smartest people once I know what that is.

#15

Yes that would be good for those people that can take blood tests. However, the answer to that question would not be simple and would differ depending on the frequency of dosing.

#16

tomorrow I will take 10mg with GFJ. At the moment I am doing it once every 2 weeks. :wink:

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