Trying a daily Rapamycin Dose Change

A little bit higher, but considering the inter person variability we’re really not sure how high it actually is.
I’m trying everolimus 4 mg mixed with rapamycin 4 mg . See what that’s like.

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With the super health of PA, not surprised this dose would likely not register any side effects. Although he said “he didn’t feel anything” on the podcast, wonder about his markers shifting some. He surely would NOT comment on any marker going worse…that would blow up his orbit.

I think his patient doses are far lower, very n=1 specific.

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If anyone thinks they are on “high dose” rapamycin, consider this recently FDA approved IV injection for treatment of PEComa

  • The recommended dosage of Fyarro is 100 mg/m2 (consider that in typical transplant setting, dosing is < 15mg/m2, albeit daily)
  • Each infusion of FYARROtakes 30 minutes
  • FYARRO is given twice during a 3-week period (this means you will receive an infusion once
    a week for 2 weeks, followed by 1 week off
  • You can stay on FYARRO as long as your disease continues to respond to treatment or until your side effects require you to stop treatment

12.3 Pharmacokinetics
Absorption

Following administration of FYARRO at the recommended dosage, the estimated mean (%CV) Cmax and AUC0-inf of sirolimus in patients with advanced solid tumors were 2590 ng/mL (30% CV) and 22100 ng∙h/mL (50% CV), respectively.

You can see typical side effects here:

The company said the drug will be priced at a WAC of about $39,000 per month, or $468,000 per year.

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This product information was posted 9 days ago.

Also in the same, was posted how it is manufactured.

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This is interesting particularly since he is rehabbing from shoulder surgery. Clearly he doesn’t feel it impacts on healing…

Also I think it’s significant how much he minimises the benefits (and I think there are some else he wouldn’t continue). A total lack of hyperbole and in complete contrast to someone like David Sinclair.

The official pharmacokinetics for sirolimus show a mean half-life elimination (in adults) of 62 hours (range: 46 to 78 hours) which is extended in hepatic impairment (Child-Pugh class A or B) to 113 hours.

What does this mean? It means rapamycin has first order kinetics, so the rate of metabolism / degradation is directly proportional to its concentration. What does that mean? It means that for people who don’t have liver failure (in which case the half life would be so ridiculously long that it almost wouldn’t matter how you took it) that taking a given dose (e.g. 6 mg) once a week will result in a lower trough level at the end of that week than if you spread the dose out evenly. (Sorry if this isn’t totally obvious to you, but I can assure you that it is to anybody who went to med school and learned pharmacokinetics.)

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Just to be clear, 6mg/week would result in a lower trough level at the end of that week than if you took 6 x 1mg/day? I would agree.

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Transplant patients have no choice, of course, but outside of that space the closest I have seen to a recommendation for “daily” dosing was Dr. Blagosklonny saying “I see nothing wrong with a daily dose of 1 mg per day for 6 days.” But he went on to say “This is not very popular now. What is popular now is once weekly dose, mostly based on the right reasons, of course.” For what it’s worth, he seem to favor high doses every two weeks.

He did say a little later that he had recently switched to 1 mg every other day. But he had a specific reason that he did not want to share. So I guess it may depend on what disease you are trying to prevent.

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