Biocon sirolimus has film coating, so the increase in bioavailability compared to compounded powder is from something else if true.
Serum concentration and immunosuppression (via mTOR inhibition), should be pretty well understood in the literature and the individual differences. Meaning, how to detect whether an increase in serum concentration is needed for a patient, otherwise transplant rejection would be the measurement which wouldn’t be practical. So I bet there is some way to know whether a higher serum concentration is needed for adequate mTOR inhibition.
PSA: Brian Kennedy seems to wonder about difference in side effects of rapamycin + CYP3A4 inhibition (using i.e GFJ), compared to rapamycin only. So using rapamycin only might be superior. For those that do that.
For now, for me, there are too many moving parts to connect # mg taken per 1 or 2 or 3 weeks with longevity effects on me. Through trial and error, feeling my way through the minefield, I have found a dosing that works for my goals.
But would like to know…:
does fat taken with rapamycin to increase absorption have the same effect as taking more rapamycin?
does gfj before rapamycin have the same effect as taking more rapamycin?
do other mTOR inhibitors (fasting) used at the same time increase the effects?
do mTOR activators (weight lifting, protein) used at the same time as rapamycin reduce the benefits?
is a small periodic dose providing any life extension benefit as seen in animal models that use massive and more frequent dosing?
does my gut health affect my absorption of rapamycin, and does it change over time?
does my body get used to rapamycin (tolerance)?
does going to zero blood rapamycin reduce symptoms without reducing benefits?
do negative symptoms have anything to do with benefits?
So, for now, for me, I take as much rapamycin as I can without significant negative side effects. I am not willing to take endure more side effects for an unknown longevity benefit (I may be so far below an effective dose that I’ll get no longevity benefit).
I can live with the side effects I get now to get immune system benefits: No sickness. No allergies. Low chronic inflammation. It’s all by feel. If I didn’t have side effects or positive effects, I’d take a bigger dose, but not more frequent (go to zero, I think is important).
No, the coating is for improving tablet swallowability and acts as oxygen and moisture barrier.
Rapamycin is a BCS class II drug with low solubility and fortunately high permeability.
Therefore, Pfizer is using Rapamycin nanocrystals for solubilization.
It is difficult to say if Rapamycin dissolved in DMSO will be more bioavailable than Rapamune or have the same or even lower bioavailability. Rapamycine in DMSO will precipitate in the gut without stabilization and bioavailaibility will depend on the morphology of the precipitated Rapamycin. My guess is that bioavailability will be as low as standard Rapamycin powder.
This may be a semantics issue… in Rapamune’s case they use Elan Pharma’s nano-crystal technology to overcome the bioavailability issue: Rapamycin and NanoCrystal Formulations
The generic manufacturers don’t want to pay Elan the royalty so they’ve developed their own coating/protective method that provides much the same bioavailability benefits (which is sort of equivalent to enteric coating, though I’m not a pharmacokinetics expert).
So the net effect is the same - bioavailability for both rapamycin and generics are good, though better by about 30% for rapamune at 10X the price of the generics.
From a layman’s perspective it might be a sematic issue.
But solubilization and targeted delivery (enteric coating) are different formulation issues. From a formulation perspective it’s a day and night difference.
More than 50% of new small molecules fail in development costing innovators billions of dollars as they cannot be solubilized. Enteric delivery is different and no issue at all.
No, they don’t use coatings. They use a technology called solid dispersions for example.
I didn’t see anything about enteric-coated capsules. Only Ageless’s compounded tablets. Did you see something I missed?
I have been compounding myself (for over 5 years) and putting in enteric coated capsules since reading about low bioavailability of compounded rapamycin here.
I tested levels at the outset (no capsules), but haven’t bothered since.
So you say they may not even had any coating? Well big f’n surprise then in that case!
Anyways, I will not waste time guessing what the paper should have addressed much clearer. It is a mess through and through and should have been asked for big changes in the review process, but this is the state of mediocre science now.
I tried now intra nasal, rectal, and enteric coated, tested the coated pills with methylene blue inside, warm vinegar as stomach acid outside, seemed to hold the blue in over an hour, but then, 20mg rapa had no side effects that way!
Just too many unknowns with the oral route, and then the rapa lands in the food in the gut anyways… so I gonna go back to rapa and spermidine rectal after two days fast. That absorption is 100% and the grapefruit does its job in the liver without contacting the rapa in the small intestines.
I’m sorry if I triggered you. I was only trying to put this paper in some context. Carry on doing whatever you feel is best, for whatever reasons you feel it’s best.
@msmccor100 I’d say we have enough info to know the guardrails of safety. That opens the door to self experimentation. Just don’t do too many things at once so you can tell what rapa is doing in blood markers, visible symptoms (skin, mouth), sensations (tiredness, euphoria, slowness to recover), and other infections (respiratory illness, re-emergence of viruses (herpes, etc).
Find a level of negative side effects you can live with (I don’t accept anything beyond feeling tired for a day) and watch for benefits (fewer allergies, colds, chronic inflammation).
Pull and push on the various levers to find and stay at a level of rapa that you like in results and hope for unseen benefits.
yes yes, I was really triggered, sat in the fetal position for hours, as can clearly be seen from that I wrote about methylene blue and vinegar, and abbreviations like “mg”, pure micro aggression.
what is it with people on this forum actually being triggered into emotional nonsense responses for usually no discernable reason whatsoever???
Is it because I am not interacting on an actual science forum as I was still 15 years ago, have medical forums always been this way, or have years of peak wokeness and Covid madness and all of that in the West really have had such a deeply detrimental effect on people’s rational capabilities?