Hair Loss - Let's carefully specify the meaning of a "local" effect!

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Let's carefully specify the meaning of a "local" effect! (Topicals)

posted by RonLev, 27.05.2008, 16:52

» » » Did you miss the whole point of my previous posts?
» » » I demonstrated to you with the graph from the Chen
» » » et al study that the effect of the topical
» » » flutamide was absolutely, positively NOT concentrated
» » » at the point of application. I took pains to point out
» » » that the results on both flank organs were IDENTICAL,
» » » even though the drug was applied only to one flank organ.
» » » Now do you understand the point that I've been making all along?
» » » The flutamide was acting in those rodent studies EXCLUSIVELY
» » » by a systemic route.
» »
» » Likewise, you are missing my point; I am not concerned about systemic
» » activity at the flank organ--I already acknowledged that flutamide is
» » systemically absorbed. What a dermatologist wants to know is: what is
» the
» » activity of flutamide at the skin site of administration and what
» happens
» » to that activity in the skin when the dose is titrated downward so that
» » systemic activity is extinguished? (That was not the objective of
» Chen's
» » experiment.)
»
» Ahhh...but that _was_ an objective of Chen's experiment! ;-) I think now
» you're also beginning to understand why I made such a big point before of
» the fact that Chen et al tested THREE separate doses: a large
» dose which strongly reduced flank organ size (identical effect on both
» sides); a medium dose which moderately reduced flank organ size
» (identical effect on both sides); and a small dose which had only a
» very minimal effect on flank organ size (identical effect on both sides).
»
» Sorry about pressing you on all this, but there's just no way to put a
» favorable "spin" of any kind on the animal experiments with topical
» flutamide. They demonstrate that (1) topical flutamide works EXCLUSIVELY
» by a systemic route, and (2) titrating the dose up or down doesn't alter
» the systemic nature of how it works.
»
» The animal experiments are clearly DISASTROUS for anybody who wants to
» develop a topical flutamide product for human use. Any rationale one can
» conjure up for how such a product might be great for humans is soundly
» contradicted by the results of these animal experiments (with the possible
» exception of the Sintov study, as I explained before). All you can do now
» is hope against hope that topical flutamide works by some substantially
» different mechanism in humans than it does in rodents; and frankly, I
» consider that to be a pretty weak foundation on which to develop a new
» product for human use. It doesn't inspire one with confidence.
»
» Bryan,
I appreciate your spirited and scientifically rigorous rebuttals. I would only add as a coda to this discussion that many drugs in this field (and I am including ALL hormonal modulators in this discussion, not just antiandrogens for treatment of hair disorders) are developed with an acknowledgement of some risk as a part of their side effect profile. As I mentioned in response to Benji's unfortunate experience with finasteride and dutasteride, even well-established, fully FDA-approved drugs will not pass muster by your standard. That is not to say that your standard is wrong, it is just that the state of the art currently puts us in a position where antiandrogenic control cannot be absolutely locally restricted. If you want truly effective control of DHT in the here-and-now, this is the risk that patients and their doctors must weigh, and for most the benefits outweigh the risks.

RonLev


RonLev is located in [NA] and he is available to meet: NO

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