Rapamycin enteric coating vs powder bioavailability

Dr. K answered by question by email. Sounds like the powder form might be greatly inferior:

"I thought we addressed this in the AMA, but here are my thoughts on the enteric coating.

The generic tablets (Rapamune, sirolimus) that have the characteristic triangle shape should have comparable bioavailability and are formulated for good uptake. The reason the mouse ITP used a special enteric nano-formulation (eRAPA) is because the raw powder is unstable at gastric pH. I have heard of at least one case where compounded rapamycin in a capsule had very poor bioavailability compared to the tablets, likely due to this reason. Hope that helps.

Matt"

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This is probably very true. I just increase my dose, my powder is so cheap. I am looking into enteric coated delivery, but yet another variable.

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Most all of India’s API’ all come from China…I didn’t know that.

But if you’re just absorbing a fraction of the powder/capsule dose (and who even knows what fraction?), and that’s assuming the chinese powder is actually 100% rapamycin in the first place, it completely totally throws off any kind of dosage guesstimation.

I’ve been buying rapa capsules from a vet for my dogs, but clearly I need to find a way to get them the tablets now, too, since dogs’ stomach environment is even more acidic than humans.

Blood Sirolimus will be my guide. I already confirmed it’s Sirolimus, other thread. Many others before me are using same vendor, but I take nothing for granted, I will need blood tests to verify.

I am planning on doing a blood Sirolimus panel shortly. Will measure time zero trough (I am doing weekly no GFJ currently), and then do 4 or 5 tests post dose, 30min, 60 min, 90 min, 120 min, 150 min post dose to see if I can capture approx Cmax.

The enteric will bypass the stomach and empty into the lower intestine. This is another variable I’ve parked to the side.

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BTW if stomach acid is the culprit, it should be possible to significantly increase absorption of a once weekly dose of rapamycin by pre-medicating with a stomach acid reducing med such as famotidine, where one dose in the evening followed by a second dose in the morning increased gastric pH from 1.3 to 6.6 (!!!)

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That is very interesting indeed.

But that’s yet another variable and med with what level of controllable efficacy? And I cannot even imagine the disruption in the gut microbiome messing with homeostasis pH?

If not using Pharma grade tablets, I think it would be far simpler to just bypass the stomach, and use good quality enteric capsule with known delay in emptying until reaching lower intestine?

Maybe, if the enteric capsules actually work as advertised. Would a once weekly dose of famotidine (with a quick elimination half-life of only 3 hours) cause any kind of disruption of intestinal flora?

In any case, yes I agree it seems more straightforward to try the enteric caps first to see if they work before introducing yet another medication variable. From what I’m reading, it seems important to take the enteric caps on an empty stomach since food might increase gastric pH enough to cause the caps to open in the stomach.

I think these enteric capsules have been around for a long time, I think they work. Certainly would want to do a careful vendor selection and rigorous enteric capsule/Rapamycin experiment. Like I said, after my next Rapamycin powder experiment, I will revisit enteric coated capsules. I shudder at messing with my stomach pH.

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Yes - but its a concentrated industry like most industries, so for any given API (Active Pharmaceutical ingredient) - most of the supplies probably come from 4 or 5 vendors. And - for each API - the different final product manufacturer in India will have different quality controls both on incoming APIs from china, and also in their own production processes… so still lots of variables go into the quality of the final product we buy.

And - as far as buying powder from china - anyone purchasing small amount of powder (e.g. under a kilo) - you’re most likely going through a middleman and they won’t tell you the actual manufacturer… so lots of blindspots with regard to quality for individually purchased powders… if the vendor says they are selling materials they produce themselves, I would find that even more scary because any vendor selling grams of sirolimus to an individual has to be an extremely small manufacturer - and generally in any market, the vendors that have under 1% of the market, are the very poorest in terms of quality control. They just can’t compete given the volumes they produce. Same with most manufacturing industries.

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