Concerns on improving Cmax and plasma halflife

Hi there,

Is there a way to get some hints that raising Cmax and plasma halflife is positiv for longevity purposes?

I have read about improving Rapa’s bioavailability with, for example Ombitasvir+Paritaprevir+Ritonavir, and, that that will increase Cmax, AUCinf and, plasma halflife.
So what is the thing that causes the benefits for health and lifespan? Is it the elevated blood levels of sirolimus once a week and Cmax is totally that thing?
Or do we want a continous plasmalevel?

The dose regime for organ transplantation patients is daily up to 4mg sirolimus. In that case, they have moderate Cmax peaks and a continous blood level.
For longevity purposes most people take a relatively high dose once a week. Here we have a decreasing but also permanently present blood level of sirolimus but with a much higher peak in Cmax than in organ transplant patients.

So I am a bit suspicious if bioavailability improving medicines will be a good thing for us. In case of GFJ, we only improve the Cmax. In case of Ritonavir we also increase the plasma halflife which might, from my point of view, be detrimental.

Any ideas?


Effect of a ritonavir‐containing regimen on the pharmacokinetics of sirolimus or everolimus in healthy adult subjects

Following co‐administration with the 3D regimen, the everolimus Cmax and AUCinf increased to 4.7‐fold and 27‐fold, respectively.

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