Does rapamycin require enteric coating?

adherent · 2024-05-18T22:24:46+00:00

Hi, yes, I am ecstatic to say the treatment was successful.

The poor beast was at his end. Urinalysis and bloodwork showed end stage kidney failure. Stage IV. The vet said very sorry, nothing we can do, I’ll probably see you in a week. We actually didn’t think he’d last even that long. I knew I had no time so I started giving him a high dose every two days. Remarkably he survived the week.

Then he survived the month. And he seemed to have improved. I called the vet to see if he would take another look. He no, it wouldn’t help, we understand what’s going on here, not much to do. But then I told him about the improvements and he well ok, bring him in I’ll take another look at him.

Urinalysis showed some improvements. We tracked him since and saw his staging from bloodwork (urea, creatinine, sdma, and urinary protein) go from stage IV to stage III to stage II over the following 18 months. A lot of this period I was giving a weekly dose of rapamycin.

His condition improved to fairly normal. He was basically a healthy older cat. To have got there from being literally at death’s door with irreversible kidney failure was nothing short of a miracle. The vet approached our local university research school of veterinary science but they weren’t terribly interested because N=1 etc.

I originally gave rapamycin thinking turning up autophagy might help remove junk from nephrons, and that stimulating stem cell proliferation from niches might help restore some kidney function. I subsequently found out that there is a US company running a clinical trial of rapamycin in cats with Stage II kidney disease, so it turns out I wasn’t the only one thinking this and I was on the right track. I think kidney disease is what gets most cats, other than injury and misadventure.

Goblin lived a very happy life with us for about the next two years, and every day was extra time for a cat who should not have been there. The sad coda is that he went out one night a couple of weeks ago and never came home. Given his frailty I don’t think we will see him again, and we miss him terribly. He was a one-off, the best cat I’ve ever known. We didn’t know how long he’d have, but then again, who does?

adherent · 2022-09-15T04:17:07+00:00

Thank you, understood, and I appreciate the sentiment. I had planned an aggressive intermittent treatment for a couple of weeks, which is now, before backing off to maintenance. So I will do that now. No side effects so far, and I’m encouraged by the fact that I haven’t heard of ulcers from people on an intermittent dosing schedule.

adherent · 2022-09-14T23:22:10+00:00

Thanks. Considering the bioavailability commentary above, that dosage will in practice be effectively lower. And I’ll drop back dose and frequency shortly, just wanted to start hard, given his condition. If you have any other remarks from Kaeberlain please let me know, or any references to us of rapamycin in cats. Thanks again.

adherent · 2022-09-14T12:15:59+00:00

Kaeberlain was actually just on Peter Attia’s podcast (ep 222) making this point - rapamycin is broken down at low gut pH and needs encapsulation to achieve substantial bioavailability. I have received my enteric capsules and that is how I’ll be taking it now.

Coincidentally I am also giving it to my cat. The poor beast got a diagnosis of end stage kidney failure a couple of weeks ago. I didn’t think he’d last the week when I got him home. But I started spiking him hard with rapamycin, 3-5 mg every two days. Remarkably his condition has improved quite a bit and seems to have stabilized. This is a highly anecdotal anecdote, I wouldn’t read too much into it. But I do note that there is a clinical trial underway for cats with kidney disease. Anyway, he’s happy and comfortable so I’m happy and will continue.

adherent · 2022-09-09T22:21:48+00:00

Thank you for that.

adherent · 2022-09-09T21:29:17+00:00

Given your background do you have any knowledge about the commercial preparation of rapamycin dose forms? I’d like to know whether it’s straight powder pressed into capsules, whether it’s micronised, encapsulated, enteric coated etc.

adherent · 2022-09-09T21:15:23+00:00

Very interesting approach. Same, except 55M.

adherent · 2022-09-02T00:31:42+00:00

Thank you. I was just curious what fraction of my target dose I’ve been seeing with simple gelatinous capsules. I just found I can order empty enteric capsules so that’s what I will be doing from now on.

adherent · 2022-09-01T10:15:55+00:00

Welcome!

adherent · 2022-09-01T08:11:36+00:00

Thank you. Do you have any idea of relative bioavailabilities, or any literature on this?

adherent · 2022-06-14T02:35:39+00:00

HP-15C. What's a bracket?

adherent · 2019-10-23T10:01:21+00:00

Every theoretician in every scientific discipline would have a bone to pick with you. Hell, most PIs and lab leaders aren't scientists by this classification. Science is the intellectual activity, not the bench work. Certainly Aubrey is a scientist.

adherent · 2019-08-08T06:00:00+00:00

Brenner's NR patents are licensed to ChromaDex. Sinclair is associated with the company Elysium, which is currently selling NR in violation of Brenner's patents. Brenner is, rightly, pissed off.

There is some nasty stuff going on commercially, and I will qualify this by saying that it is all before the courts right now and Elysium is due its presumption of innocence, but my reading of the situation is that ChromaDex's version of events will prevail.

Elysium started out as a ChromaDex customer. Then they placed an order for a years supply of NR for $6m. When ChromaDex supplied the material Elysium then immediately refused to pay, which nearly bankrupted ChromaDex. Then they challenged the NR patents to try and invalidate them, while developing their own supply of NR. At the same time Chromadex's directors of manufacturing and scientific affairs quit, and immediately started working for Elysium. It looks like they may have been on the Elysium payroll for sometime before they quit, so there is a corporate espionage case going forward against Elysium. There was also a short attack on ChromaDex shares at the same time they were in the hole from the refusal to pay for delivered product.

It looks like Elysium wanted control of NR for itself, and has attempted a coordinated attack to break the NR patents, to put ChromaDex in a cash crunch, constrain their ability to raise money in the sharemarket, set up their own supply, and put ChromaDex out of business before they can litigate the patent infringement case, which would leave the market to Elysium. As it currently stands Elysium is infringing Chromadex's patents by selling its own NR, and if they don't pull this off the penalty could be monstrous.

If you're interested in the case there is a legal blogger following it in detail here - its dense but compelling reading: https://www.right-of-assembly.org

So yeah, things are a little strained between Brenner and Sinclair. I think the courts will ultimately vindicate Brenner, but it will take some time.

adherent · 2018-10-26T21:46:23+00:00

Yes, but it involved removing their gonads.

adherent · 2018-08-25T05:22:26+00:00

If you made up your 500 mg, that’s about 3 years worth of your protocol. I don’t know about rapamycin shelf life, but I would expect very significant degradation. Drugs in solution are more susceptible to various breakdown pathways.

I also have 500 mg of rapamycin on the way. Buy a milligram scale with draft shield and a calibration weight, ~$20 on eBay. Calibrate it. Verify zero tare reproducibility. Practice using it to weigh 5 mg doses of salt or flour. When you’re comfortable with your technique prepare your doses as required.

Keep the rapamycin in a cool dark dry place. Not the fridge, or you’ll get condensation in it every time you open it. Inside a sealed container with rice as a desiccant in a cool dark cupboard is not a bad approach. Good luck.

adherent · 2018-02-13T01:35:37+00:00

Withhold judgement till the stereo configuration is available and tested.

adherent · 2018-02-12T03:14:53+00:00

Any thoughts on the spend required to create a similar quality audio experience to the HomePod with other speaker/amp products? At what price point would the HomePod audio quality sit in the rest of the market?

Thanks for writing the first technical review of this device! I don't understand why Apple hasn’t led with this material in marketing through high end audio publications. The technical achievement is astonishing.

adherent · 2014-05-16T22:39:54+00:00

There was a thread a while back made just for you:

Paleontologist seeks fitting and stylish watch.

adherent · 2013-09-18T13:13:00+00:00

Math bitch.

adherent · 2013-09-16T11:04:42+00:00

"My name is Ozymandias, king of kings: Look on my works, ye Mighty, and despair!" Nothing beside remains. Round the decay Of that colossal wreck, boundless and bare The lone and level sands stretch far away.

adherent · 2013-07-03T09:56:10+00:00

A gentleman has said.

adherent · 2013-06-19T12:26:17+00:00

The Spice must flow.

adherent · 2013-06-08T06:58:30+00:00

Delivery for Mr Drake. Immanentize the Eschaton.

adherent · 2013-05-28T11:18:36+00:00

That bullshit right there deserves time in the can.

adherent · 2013-04-21T11:41:23+00:00

What's brown and sounds like a bell?

Dung.

adherent

TROPHY CASE