The Key issue of Dosing Levels and Intervals for Best Rapamycin Outcomes

Here is a post with information about the blood sirolimus test, you need to call them and specify the test number. It may take a bit of work - some the lab test people don’t seem too familiar with it:

See this post for details on how to identify the test (you have to call their lab test customer support, its not yet listed on their website): Life Extension Blood Sirolimus Test

also mentioned here:

Hi Rapamycin enthusiasts,
I’ve encountered a delay in getting my book published. New books need to get a registration number and bar code from the Library of Congress. This process has traditionally taken 8-10 days. Currently, due to COVID and staffing problems, the wait is 1-2 months. Stay tuned…I’ll shout out as soon as Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome is available. Healthy regards, Ross

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Anyone planning on doing a Sirolimus test, play very close attention to the pharmakinetics. There is a very rapid peak of blood concentration (1st 2 hrs), and then rapid drop off. See Figure 1 in attached paper.

https://sci-hub.se/https://doi.org/10.1016/S0009-9236(97)90192-2

Depending on dose, and time of blood draw after dosing, you might not get a meaningful signal.

Perhaps schedule an firm appt, and take your dose a couple hours before.

Yes - given the rapid rise and fall I’m not sure there is much value in trying to get the peak blood sirolimus level. The trough level - via a blood draw just prior to the next dose of rapamycin - seems like the most useful to make sure you are waiting long enough before taking the next rapamycin dose, and thereby minimizing risk of mTORC2 inhibition.

Agree with your logic for maintenance reasons, combined with side effects.

But if you’ve never had a Sirolimus blood test then:

  1. Do you even know for sure what your’re taking is Sirolimus, especially those of us sourcing overseas? There could be many people who have no idea if they are taking any rapamycin at all.

  2. Bioavailability is very poor, so unless you’re taking a high dose, you might not even catch the signal at all if you do the blood test before next dose.

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Fair points. The lab analyses I’ve seen of the generic sirolimus / rapamycin medicines out of India seem to suggest they are of reasonable quality, but the sample size is very small - so yes, the idea of the peak blood sirolimus levels as a proxy for validating at a very rough level the dosing / purity of the tablets sort of works (though without information on contaminants its still far from ideal).

Given the low price of generic rapamycin, I don’t think there is too much of an incentive for rogue pharma resellers to sell “fake” rapamycin with low or zero levels of the actual sirolimus (it seems more likely they would target the high-priced name brand drugs that they could sell for a much higher price).

I suspect the bigger risk is the potential for contaminants like nitrosamines like we’ve seen even in generic versions of metformin sold in the USA and other western countries (as Katherine Eban has highlighted in her book)

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This is why I’m prepared to pay more and get Rapamune (Pfizer)

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You have a reasonable cost for “original” Pfizer brand Rapamune.

30 tablets 2mg lowest price I see is $1,880.00

I paid £400 for 100x1mg

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Interested in having a straw poll on forum members’ mg/kg/week

I’m now up to 8mg/wk at 76kg so a little over 0.1mg/kg

Hi Dr. Ross Pelton! I first read about Rapamycin in an article published in Life Extension magazine and they also offer your book at lef.org
I’m very excited to read this book! I think it may have some of the information that we are all looking for in this forum. I am learning a lot here!
April 22nd 2022 is when the book becomes available thru the life extension website (I think)

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i weight 160lb (40 years old) and usually do 7mg a week

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its $5-6 a mg

FWIW…

62yo - male
190lb, 6’1" height
6mg{currently 2mg x3}
Eat one GF wait one hour, then take with sardines in OO

Have been think/considering to increase the dose.

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I currently am taking sirolimus every two weeks, at a dose of ~0.35 mg/kg.
I decided to do biweekly dosing after reading this article and doing a rough extrapolation of the half-life of sirolimus in humans vs. mice.

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system - Lamming Lab.pdf (574.9 KB)

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I think that’s the highest dosage I’ve heard of. It would equate to 26mg/fortnight for me

So using this data to extrapolate from MKs TRIAD dog dosing you get:

0.15mg/kg/wk x 0.541 = 0.081mg/kg/ wk

Or 6mg for a 75kg individual

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Has anyone else looked into the effectiveness of the actual grapefruit rind and peel in contrast to the fruit and juice? I usually blend one-half of a white grapefruit, skin and all, before taking my rapa dose. I use a natural low-glycemic sweetener to mask the extra bitter taste. (Is “bitter taste” a chemical hint?). I base my method on a few studies I’ve come across that seem to indicate it may be beneficial. I don’t like getting a bunch of sugar from the juice either and it might be more reliable than bottled and processed juice. Identification of epoxybergamottin as a CYP3A4 inhibitor in grapefruit peel - PubMed

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The effect of grapefruit juice on drug disposition

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As usual, we need a study that shows peak and AUC effects of GFJ and now GF peel. It’s hard to say what the equivalence between the two might be.

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