Why is it possible for mice to take high rapamycin doses daily?

#1

In this study male mices took a daily dose of 8mg/kg/day for a period of three months, and it resulted in 13% increase in mean lifespan.

If we covert the dose to human its around 46,6 mg daily for a 75 kg person.

8mg/kg/day = 8 x 0.081 = 0.648 mg/kg/day = 0.648 mg/kg/day x 75kg = 46,6 mg daily

Converting of dose from animal to human is based on this study:

How is it possible that a male mice can take so high dose daily with a positve effect but that high dose is not good for humans? The standard dose for example for immunosuppressive effect on humans are around 2-5 mg daily. Here is the source for the dose on immunosuppressive on transplant patients:

What am I missing and not understanding regarding the differences between mice and human?

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#2

I think that I’ve heard before that mice metabolize rapamycin very quickly (i.e. short half-life in their blood stream) - so its less of an issue in terms of daily dosing, compared to humans.

I think this is image presents this general idea:

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#3

Found it… here is the quote:

Importantly, the clearance of rapamycin is much faster in mice than in humans. For example, in mice levels of rapamycin drop 20-folds the next day after injection,whereas in humans its terminal half-life is about 2.5 days. It was estimated that a 1.5 mg/kg injection in mice corresponds to the therapeutic oral dose in humans.

Full Paper (PDF) Here:

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

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#4

2 posts were merged into an existing topic: Rapamycin - for Cancer Prevention

#5

Great sharing! Regarding the below quote.

It is also interesting that they lift up injection dose and oral dose. In the quote below. What is the therapeutic oral dose?

It was estimated that a 1.5 mg/kg injection in mice corresponds to the therapeutic oral dose in humans.

Also regarding the study about converting dose from mice to human when it comes to rapamycin is not correct. Is there some other way to get the converting more correct between mice and human? Or can we calculate it by using the numbers in the quoute you posted. This one:

Importantly, the clearance of rapamycin is much faster in mice than in humans. For example, in mice levels of rapamycin drop 20-folds the next day after injection,whereas in humans its terminal half-life is about 2.5 days. It was estimated that a 1.5 mg/kg injection in mice corresponds to the therapeutic oral dose in humans.

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