[quote=“Bfaith1642, post:104, topic:85”]
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In a recent interview with Peter Attia who asked what keeps him up at night about the study, Kaeberlein responded he worried the dose was not large enough.
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Yes - specifically, he’s talking about in the Dog Aging Study, Rapamycin trial. (and of course, most of us humans are taking a lower dose… )
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Looks like they were measuring sirolimus levels for this not so successful osteosarcoma study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172450/
Pharmacokinetic assessment of sirolimus-treated dogs
A validated method for extraction of a sirolimus analog was used as described to extract sirolimus from 100 μL of each blood sample by means of protein precipitation with 0.2M zinc sulfate followed by liquid-liquid extraction with 1 mL of ethyl acetate.26 The sirolimus concentration in each sample was determined by use of liquid chromatography-tandem mass spectrometry with tacrolimus as an internal standard as previously described.18
Further, the majority of dogs demonstrate measured sirolimus blood levels below 10 ng/mL. The AUC/dose equivalents for cycle 1-Day 11 and cycle 1-Day 25 timepoints were 1499 ± 1446 [nghr/ml]/[mg/kg] and 1357 ± 1475 [nghr/ml]/[mg/kg], respectively. To assess sirolimus pharmacokinetic variability across treatment duration (cycles 1-4), sirolimus levels were measured at 2- and 8- hours post dosing (Figure 3b). ANOVA showed that 2- and 8- hour timepoints were significantly different (p < 0.0001), but none of these average values were significantly different across cycles of treatment (p = 0.4825). Within this dataset, intra-patient variability was relatively small compared to inter-patient variability, suggesting that PK differences were largely patient-dependent. The magnitude of inter-patient PK variability was underscored by the wide range trough concentrations calculated from a subset of dogs (n=78) receiving sirolimus being 0.53 to 30.98 ng/mL, which span across predicted sub-therapeutic (< 10 ng/mL) and therapeutic (> 10 ng/mL) concentrations.
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May I ask your dosing? I have a 6 pound papillon. Dr Kevin has him on .5 mg once per week. I have not found that size from any of the Indian sites. I heard other dogs get their Rapa 3x per week.
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He’s 13.5 pounds and gets 1mg/week.
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Everolimus (another version of mTOR inhibitor, very similar to rapamycin) is available in smaller dosing quantities - see the photo below. More information here: Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?. (82 rupees to the US$, so divide the prices below by 82 to get US dollars.)
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Thanks I have considered that but it is not as potent. Is it close enough to be safe for dogs?
It’s listed under company SS Enterprises on Indiamart. On Indiamart, it will be referenced as Sirolimus rather than rapamycin.
Edit: Removed second source. They apparently no longer have it. It is still listed under SS Enterprises above.
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Thanks you just saved me a fortune!
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Seems like minor differences to me but here is a paper looking at gastrointestinal pH in Dogs and humans. Dog stomach pH is slightly higher (more basic) and Dog intestinal pH is also slightly higher (more basic). This suggests to me that if anything sirolimus would be more stable in the dog gi track resulting in better bio availability.
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Let me know how more frequent dosing works.
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@Pattyg Will do! I’d prefer the 0.5mg for myself as well tbh. I have quite a bit of the 1mg on hand right now so I’m probably a few months away from reordering.
Does anyone know if Zydus manufactures sirolimus in 0.5 mg?
India Mart has several vendors that listed, but all reply that they only have 1 mg and 2 mg.
Unfortunately it seems the Indiamart vendors who were providing 0.5 mg pills no longer offer them.
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If you have a small dog, and are looking for sub-1mg dose tablets, I’d look at Everolimus. There are vendors, including Zydus, that provide 1mg and sub-mg tablets in that form: Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?
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Thank you. Will do a deep dive on Everolimus. One Indian pharma respondent suggested the 1mg sirolimus be split with no comments on bioavailability 
. Triumvet is using a patented coating. Sounds like there may be evidence of higher oral availability of everolimus. Lots of questions about equivalent dosing.
I think I could get more comfortable with Everolimus if there was/were:
– more clarity regarding MTorc2 inhibition
– available reports on purity
– more clarity on oral bioavailability and dosing
RapAdmin, did you ever decide to incorporate everolimus into your regimen?
With all of these outstanding questions, I’d prefer to stay closer to the TRIAD study standards, but am interested to know if anyone else is dosing their dog with everolimus.
For now, splitting a Zydus or Biocon 1mg tablet and placing into AminalBiome’s #4 delayed released capsule seems to be a reasonable option.
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I probably have the weirdest story about dog dosing. We’re both pretty new at this - two months or so. My first prescription was supposed to be 5mg doses, my own recco to my MD with which he agreed, but the compounding pharmacy screwed up and sent me 12 x 100mg (!) capsules. I talked to my doc and we agreed on 5mg, and asked them to exchange. They said they had no use for the first batch, sent me a refund (Godawful expensive, it was), said to keep the others, and sent 12 x 5mg caps. I was aware of both Matt K.'s dosing and Dr. Kevin’s, and I thought Dr. Kevin might be a bit much with 3X weekly. I used a precision scale to weigh the capsule and contents of a 100mg cap, thinking that if I could divide it into 20 doses I’d have 5mg each to give him. BUT there was not enough mass/content in each to divide into 20 doses. So, he is getting an inexact and possibly excessive dose once weekly. I know what it weighs, and know it is about 1/5 of the contents of a 100mg - but no idea how strong it is. So, we’re on week five or so, with no bad symptoms, but no great changes either. He’s a big healthy ten-year-old, and is still big and healthy. Me, I’m taking the 5mg/wk and feeling good but nothing standing out - yet. I’m 75, ex-bike racer, bodybuilder, active pilot - some orthopedic issues from trashing myself, but still working out moderately and in excellent shape and weight . Both of us use lots of life-extension type supplements, and have for years. Great to be in your company - this is fun!
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Hi, I’d be most concerned about 2 major issues. 1) the quality of the compounding pharmacy. Giving you 100mg capsules is a MAJOR screw up. That could have killed you and/or your dog. How much can you trust that they actually know what they are doing? 2) how much of the compounded capsulized rapa is being absorbed? See other extensive discussions on the forum regarding poor absorption from compounded rapamycin capsules as opposed to tablets
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