» Bryan,
»
» I don’t see where we disagree. Flutamide has a systemic effect, end of
» story. But in biological systems, dose is everything. At doses used in
» dermatologic practice, the distal response has not been demonstrated at
» the doses used.
If I’m understanding you correctly, I think you’re grossly misusing the term “distal response” here! :no:
In the context of whether or not an antiandrogenic drug has a “local” effect where applied topically, flutamide has been demonstrated NOT to have any local effect in most of the existing studies; only in the (questionable?) Sintov study has there been a claim to the contrary.
What you seem to be talking about above is something entirely different, though, which is whether or not you can get a decent antiandrogenic effect from flutamide without nasty side effects of other kinds, REGARDLESS of how you get the flutamide inside you. If that’s really all you’re claiming here, and you’re admitting that flutamide will inevitably go systemic regardless of how you apply it, then there’s no particular reason to use it topically. You might as well just go ahead and SWALLOW it!
Certain other antiandrogens do in fact have local effects, though. Two obvious examples are spironolactone and RU58841. When those antiandrogens are applied to only one hamster flank organ, ONLY that one flank organ is affected. The other one on the other side isn’t. In other words, there is no “distal response” at the site of the other flank organ, antiandrogenic or otherwise.
» For example, women taking oral doses of Flutamide at 250 mg or
» less do not manifest changes in fertility, sexual function or elevated
» liver function tests, which are the hallmarks of flutamide toxicity–and
» those systemically absorbed levels are 25 times what we see with topical
» administration (@62.5 mg).
Well, there you go: so are you really admitting that topical flutamide (even when used in the form of your new product) has no local effect at all, and it’s entirely systemic?? What exactly is the point of using it topically in the first place?? Why not just go ahead and swallow the proper dose of flutamide?
.