Improve Bioavailability of Rapamycin (2)

[adriank]

0.1 or 0.2ml? Question is how much will it show up in the blood test. I suspect it might help the immediate area you apply but I doubt it will travel far beyond that.

[Karel1]

@adriank. Please give some scientific underpinning of your doubt.
Please take notice that there are several systemic drugs being applied via the skin like estraderm, Transderm Scop (scopolamine).

[adriank]

I haven’t read anything that states otherwise… it would be nice if it did. After all I am making my own spray with transcutol and rapamycin. My psoriasis less obvious but there can be lots of reasons.

[RapAdmin]

@Karel1

The question I would like to pose: rapa is probably very soluble in dmso. Possibly a full dose can be dissolved in just 0,1 or 0,2 ml dmso and after application to the skin reach circulation for a very high percentage bypassing poor adsorbtion in the gut and first pass metabolism in the liver.
Though dmso is a very potent substance in its own right local side effects may be minor and the garlic odor may be acceptable.

I’m not aware of any studies with rapamycin and DMSO for skin absorption, though I suspect like you that it would be effective at some level (how much I’m unclear on). But there are reasons to be concerned also, in terms of the effects on the skin.

I think DMSO is a little more aggressive in terms of its results than most skin companies want… here is a quote from a cosmetic dermatology textbook:

Another solvent, dimethylsulfoxide (DMSO), by contrast, is relatively aggressive and induces significant structural perturbations such as keratin denaturation and the solubilization of membrane components

See full info and quote in this post: Rapamycin for Hair Growth and Hair Pigmentation - #320 by RapAdmin

[Karel1]

Thank you for your info.
DMSO will cause an irritated burning feeling but I was not looking for applying to the scalp. For that application we have minoxidil lotion which is not very nice either.
The safety of small amounts of dmso is probably great as it has been proven to promote survival of stem cells in cryopreservation.
PMC11172459.

[John_Hemming]

If I am using DMSO I aim to keep it at 10% or below in water.

[Gregg_Bronson]

At what age can we start to give a dog Rapa. I have a GS that’s almost a year old.

[RapAdmin]

I waited until my dog was age 4 before giving it rapamycin (my dog is quite small, 24 lbs, so would normally (I think) have a life expectancy of around 14 or 15 years. If I had a faster-aging, larger dog (e.g. Great Dane, etc.) I would likely start earlier; perhaps at age 2 years.

See this research and data, as its likely also relevant to dogs: The Case for Starting Rapamycin Earlier in Life (e.g. late 20s) vs middle age (e.g. 50s)

Related: How Do I Get Rapamycin for My Dog?

[John_Hemming]

The same argument about dogs may apply in terms of frequency of dosing and a younger dog may have merit in having a dose once a year.

Our problem is measuring the improvement in mitochondria more directly.

[Thiago]

Hello everyone.

Any information about fiber and the absorption or rapamycin?
Let’s say a breakfast with water, 100g of oats, 20g of broken flaxseeds, 30g of vegan protein powder and some blueberries and a good portion of olive oil.

Would this be decreasing my absorption?

If I take on an empty stomach or even with let’s say almond butter, I get a huge bloating and GI pain for a day.

Thank you everyone

[RapAdmin]

@Thiago

Any information about fiber and the absorption or rapamycin?

I’ve not seen anything to suggest lower bioavailability of rapamycin when taken with fiber - so on that issue I think you’re fine. The bloating and GI pain is unusual though. So - you don’t get that when you take the rapamycin with a full stomach as with the breakfast you suggested?

[Thiago]

Hello @RapAdmin

You are correct. If I take it on an empty stomach or only with some nuts because of the fat, I have a big bloating and GI pain for 1 day, but no diarrhea.
If I take it immediately after my traditional breakfast with oats, olive oil, flaxseeds, vegan protein powder… I never have any bad feelings.

That’s why I was wondering if it would reduce the absorption. No idea.

Thanks

[R_S]

Hi, do you think that grapefruit juice still enhance bioavailability of Rapa if you take it after few days after taking Rapa. Not taking GJ and Rapa immediately together.

[DeStrider]

You should take grapefruit juice 1-4 hours before Rapamycin to get 3X more absorption.

[RapAdmin]

I don’t think taking Gfj much after rapamycin will do anything.

[DrFraser]

I agree, it is affecting primarily the absorption and doesn’t seem to do anything much with the metabolism. So getting 3 times the level is done with CYP3A4 in the intestinal wall, and thus would not benefit if the GFJ came after the Rapamycin. I’ve gone to 8 oz GFJ 3 hrs prior, then 4 oz at time of taking the Rapamycin. Doing it the same way each time works well (and w/ 1 oz of Nuts or tbspn of EVOO), and then one can get a 50 hr level if dosing q7 days, or a 100 hr level if dosing q14 days.

Here is one detailed write-up
Grapefruit juice increases sirolimus levels primarily through the inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme, which is responsible for the metabolism of sirolimus. Grapefruit juice contains compounds such as furanocoumarins, including bergamottin and 6,7-dihydroxybergamottin (DHB), which are known to inhibit CYP3A4 activity 12. This inhibition occurs mainly in the intestinal wall, leading to increased oral bioavailability of drugs metabolized by CYP3A4, such as sirolimus 3.

The inhibition of CYP3A4 by grapefruit juice is both competitive and mechanism-based, meaning that it can lead to a significant increase in the plasma concentration of sirolimus when consumed concurrently 2. This effect can be substantial, as grapefruit juice can increase the area under the curve (AUC) and peak plasma concentration (Cmax) of sirolimus, potentially leading to increased drug exposure and risk of adverse effects 3.

Additionally, grapefruit juice may also inhibit P-glycoprotein (P-gp), a transporter protein that affects drug absorption and distribution, further contributing to increased sirolimus levels 4. The combined inhibition of CYP3A4 and P-gp by grapefruit juice can lead to higher systemic exposure to sirolimus, necessitating careful monitoring and potential dose adjustments to avoid toxicity.

Due to these interactions, it is recommended to avoid grapefruit juice and other citrus fruits like limes and Seville oranges while taking sirolimus to prevent increased drug levels and associated risks (ASHP Drug Compendium [Sirolimus; Immunosuppressives]).

[adriank]

For me, after trying out GFJ and food… best time to take rapamycin is 3 hours after GFJ and food. That yields the highest level according to my bloodworks. I tried in 30 minutes intervals … 3.5 hours the result start to decline again.

[Thiago]

Are you taking on an empty stomach?
Do you do this only to save the rapamycin pills?
Thank you.

[adriank]

I have my GFJ first with my meal… and 3 hours later, I have the rapamycin with either EVOO or hemp oil … no more food.

[DeStrider]

Rapamycin is best to take with a fatty meal for an extra 0.5X absorption. GFJ is 3X. If you do both, it’s 3.5X.