Some have claimed that without an enteric coating to protect tablets from stomach acid, bioavailability of rapamycin will be nearly zero. (This was recently mentioned on Peter Attia’s podcast).
This is of concern to those like myself who are using non-enteric tablets from Indian generic manufacturers.
However there are reports in this forum and in the literature of absorbtion in non-enteric preparations being just as bioavailable as the coated tablets [0]. This seems inconsistent with the idea that it gets rapidly degraded by stomach acid!
Could it be that the solubility of rapamycin protects it from attack by stomach acid?
Rapa is very hydrophobic so is nearly insoluble in water but soluble in oils.
If there is any oil present in the stomach, I would expect most of the rapamycin to end up in the oily rather than the aqueous phase of the stomach mixture. The rapamycin would be protected from acidic attack dissolved in the oil. This is consistent with the finding that eating with an oily meal improves bioavailability [1].
It also seems possible that the rapa would just stay in solid phase and not dissolve at all.
This suggests to me that:
Non-enteric rapa tablets are probably okay to use if taken with oil, and may be just as good as enteric tablets
Possibly we could do even better by pre-dissolving the tablets in oil?
For myself, I think I will continue taking the generic Indian tablets I have, but will start taking them with a spoonful or two of olive oil.
The generic tablets from the Indian pharma companies (e.g. Zydus, Biocon) do have some sort of coating, that protects that rapamycin from the stomach acids. These drugs work fine and do not have any bioavailability issues.
The warning that Peter Attia and other medical professionals have raised is with regard to compounded pharmacy sirolimus that is just powder put into gel-caps. Those are the capsules that do not have good bioavailability (from many reports).
From what I can tell they do not. Do you have any more information on this?
At least the ones I have (made by Biocon) have a matte white appearance and do not appear to have the thicker shinier appearance that the Pfizer ones have.
The package insert describes it only as a film coating. Crushing the tablet reveals that this coating is very thin. I wouldn’t expect that this coating would have the same effects as a proper thick and shiny coating that I am used to seeing on enteric coated drugs, but maybe I am wrong.
I think you are incorrect here. The rapamune trick for increasing bioavailability is not the coating, its in the structure of the actual drug mixture. You can read more about the nanocrystal technology they use (they license it from a well-known drug technology company called Elan Pharma) here: Rapamycin and NanoCrystal Formulations
I don’t know the approach that Biocon and Zydus, etc. use to maximize their bioavailability, but it works fine. We’ve had many people here test their blood/sirolimus levels after using Zydus and Biocon tablets, and from their reporting we know that the bioavailability is good because it shows good blood levels after dosing.
But just to comment on your original posting regarding oil ingested at the time of taking rapamycin, there are papers that show that taking any type of rapamycin / sirolimus with a “fatty meal” increases the bioavailability by about 30%, so many of us here do take our dose or rapamycin with olive oil (a shot of an ounce or two) and / or sardines, or other “fatty meal”.
