The BSA method is used for determining the dose for the first use in humans, where there is no human PK data. It is really focused on toxicology, not pharmacodynamics. Many of the examples in that paper, whose authors included a cancer researcher and a toxicologist, concerned toxic chemotherapy drugs. They even go as far as to say:I used the BSA equivalent calc based on http://www.fasebj.or...fasebj;22/3/659 . I think the lifegen/weindruch paper that is discussed previously in the thread using mice @ 4.9 mg/kg, mentions that a low dose turns on a certain set of longevity genes (it discusses overlap of gene expression between CR and resveratrol, etc.).
But I *think* there is a comment in that paper mentioning that a low dose turns on a high % of these genes expressed in CR, and that a higher dose may not be ideal because it would change the expression profile or increase expression in genes not desired (if i recall properly, dont have the paper atm i am on the road).
why wouldn't you want to equate a low dose strategy to the BSA-HED used in this paper? i realize what you are trying to do in terms of plasma level, but what is the differential between human/mice such that the HED-BSA calc is invalid for resv.
It's the ADME where the BSA calculation really falls apart. It's basically designed to err on the safe side. There are undoubtedly some compounds where it works well, but from what we know about resveratrol, now well studied in humans and other species, resveratrol isn't one of them. That's why Sirtris was using such large doses in their trials.BSA normalization of doses must be used to determine safe starting doses of new drugs because initial studies conducted in humans, by definition, lack formal allometric comparison of the pharmacokinetics of absorption, distribution, and elimination parameters.