Glad the article was helpful. Looks like we ran upon just the kind of information you were needing. Here’s a similar article: The Effects of Oral Sirolimus on Insulin Dynamics in Horses with Naturally-occurring ID — University of Kentucky .
Much luck with the care of your friend!
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@COOP Probably you saw this but note that at a sirolimus dose of 0.06mg/kg (IV) they observed a Cmax plasma concentration of 277 ng/ml which is much much higher than typically being investigated for dogs and smaller research animals although levels in these animals are generally whole blood, not plasma. Not saying it is bad but just that we don’t know and others are targeting a much lower whole blood concentration.
I’m not sure whether to expect sirolimus levels to be higher in the plasma fraction of blood but at least one study suggests they are lower, in fact as much as 36x lower in normal human subjects.
Especially with the insulin concerns I might target a peak sirolimus concentration closer to 1/10th of that amount in whole blood (~ 20 ng/ml) but this too would depend on the 1/2 life. Even that would be on the high end of Cmax for ongoing studies. You might want an IV dose reduction of as much as 1/100th or perhaps even lower. Also probably obvious to you but the oral dose will likely be quite different if you go that route.
So the study likely gives you a place to start with an oral dose since oral bio-availability will likely be lower than IV bio-availability but I think you will still have to do a mini study to determine Cmax and T1/2 in whole blood. At least that is what I would do. Since we don’t really know what the correct dose is, I’d err on the conservative side of matching the dose of ongoing studies to obtain a similar whole blood concentration.
Update on the horse and rapamycin:
after studying the 2 research articles that @Paul_Moss so graciously shared, after discussing with my vet and getting bloodwork done on my beautiful mare: I have moved forward on one week of sirolimus 10mg once a day, in molasses,for one week, first dose today.
In horses: hyperinsulinemia is a real problem, esp as they age–it contributes to laminitis, swelling of the blood vessels in their hooves, which is a leading cause of lameness and death in horses worldwide. Sirolimus lowers insulin levels in horses. elevated mTor1 increases insulin in horses. mTor1 goes up as they age.
my horse’s insulin level was 42uU/ml
50uU/ml is insulin dysregulation
20-50uU/ml–correlate with clinical signs.
I also got a complete blood count, liver enzymes, kidney function, cholesterol, fibrinogen, ACTH, glucose, etc.
Anyway, I have baseline labs–
So I will give one week daily dosing, and see. It’s a really low dose. Maybe repeat some of the labs in one to three months. That sound you hear is my horse eating cash 
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I’m really interested to see how this goes. If it were I (and my wallet), I’d prefer having labs done, including insulin, in 2-3 weeks. I’m concerned that with just one week of Sirolimus dosing, the effects might dissipate if you wait 1-3 months.
It’ll also be very interesting to hear clinically, if you notice any changes, ie. gait improvement, appetite, or etc. Please keep us informed!
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@Paul_Moss thank you for that suggestion!
I maybe can put her on somebody else’s vet visit so we can split the travel fee or possibly haul her in to the vets for a cheaper deal. What I am really hoping for, is improvement in her fecal-water syndrome, which is where they have normal poops, but then some squirts: this is a mysterious ailment that seems to defy all logic and treatment: the only time it goes away is when she is on pasture AND I soak her hay: now that pasture is closed, even with soaked hay–it is back. If there is improvement with that, I consider it a win.
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That would be a nice thing and very interesting. I wouldn’t be surprised if it improves.
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You need to take into account that Rapamycin powder won’t be properly digested - so you would need to give your horse either pills or buy some formula that can be added to food (like eRapa (enterically targeted rapamycin) for mice)
@PolishGentleman I put her pills in molasses and let her lick them out–I don’t see alot of chewing, so hopefully she is getting the full pills.
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Any update on how the rapamycin for horses trial is going? Would love to hear…
I saw this in a recent substack article by “Artemy Shumskiy :
Finally, a trend that I envision to be a logical continuation of the pet longevity thesis is larger companion pet (i.e. horse) and livestock longevity extension. While some companies like Gordian are working on horse models of disease, longevity extension itself in horses and livestock is potentially a very lucrative business. With cars killing the layman horse industry for good in the early 20th century, horses are now akin to living supercars, though their HORSEPOWER (lolol see what is did here) is lacking. Nonetheless, while an average horse costs somewhere between $1000 and $10000, some purebred race horses will cost you hundreds of thousands, potentially millions of dollars. However, the time span when horses are considered “productive” is about 15 years - as such, it could be a lucrative (yet niche) to extend this productivity span by a couple of years. The livestock market could be more lucrative - sheep are only useful for wool production for 6 years, egg-laying chickens are useful for about 3 years, milk cows for up to 4 years. Nonetheless, this sector probably does not have much translatability to humans, so should be pursued only by the passionate in both longevity and agrotech.
Full article: Making longevity cool, part one - by Artemy Shumskiy
I was going to try it on one of my wife’s goats, but decided it probably wouldn’t work because the rumen is very different from the stomach and probably the only way to make it work would be injection. Not the end of the world, but would have to buy a whole different set of stuff and probably make it myself or something. Gave up.
They’re right though. Some animals are really valuable and getting a few more years out of them would make a huge difference. We owned the top producing nubian buck in the country for a few years and of course by the time you find out how good he is (daughters have to kid, etc) he’s dead. There are other expensive solutions, but if Rapa gave just a few years more it could make a huge difference.
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@RapAdmin
Update on sirolimus for horses: N=1
I decided to give her 10 mg of sirolimus once a day for 7 days and then have a month off. (4 weeks) I did this twice, with seemingly good results (energetic, easy to canter and trot).
This 3rd month, on the 5th dose of 10 mg, she refused to take it–it was mixed with molasses and an oil that’s supposed to be good for horses. I decided to suspend the remaining doses of that round as ferociously cold weather and snow was moving in, and I didn’t want to confuse things with the change in conditions or cause her any problems.
The vet is coming Saturday to “float” everybody’s teeth and I will check in with him.
I have done pre-rapa labs, and may repeat one (ACTH for Cushing’s and possibly insulin level) but it is dreadfully expensive to repeat them all. What I am looking for is insulin regulation and prevention of Cushings and laminitis, with this use of sirolimus–big deals in older horses.
Thank you for the article on aging animals, and extending their longevity.
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