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, 25.05.2008, 20:08

» » 2. You seem to have contradictory views about effectiveness. You
» » (correctly) state that flutamide has shown a systemic effect, but then
» » you assert that no local effect can be assumed without clinical
» studies.
» » However, normal pharmacokinetic partitioning requires a drug to
» traverse
» » the dermis (where the hair follicles reside) and cumulate a significant
» » concentration there before it can pass into the systemic circulation.
» » Therefore, a drug that demonstrates a systemic effect MUST have a local
» » effect, if there are susceptible receptors there.
»
» I'm going to explain to you EXACTLY what I mean by a "local" effect, so
» that there can be no further misunderstanding: when a drug has the
» intended effect ONLY where it is physically applied and not in any other
» location, then that is a "local" effect. Take a look at the following
» graph which is a part of the Chen et al topical flutamide study
» which I cited in my previous post:
»
» http://img479.imageshack.us/my.php?image=flutamide8la7.jpg
»
» As you can see, they applied three different doses of flutamide ONLY to
» the right flank organs of the hamsters, while the left flank organs
» received only a control vehicle without the drug. But both flank organs
» were reduced IDENTICALLY by the flutamide, and at all three doses!!
» Clearly, the flutamide was getting absorbed systemically, and then got
» spread to both flank organs through the bloodstream (and notice that the
» same thing happened with the topical finasteride). There was no "local"
» effect at all. And the other topical flutamide study from 1975, which I
» previously cited, had a similar result.
»
» As I said in my other post, the Sintov study is the only one I know of
» which claimed to find a "local" effect from the topical application of
» flutamide, but I find it to be less than fully persuasive. I think it's
» rather strange that you and your company would go to so much time and
» trouble to develop a very expensive product based (mostly) on such rather
» flimsy evidence as the Sintov study (and I'll add here that any evidence
» for using topical dutasteride is ENTIRELY absent from the medical
» literature).
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. 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).

RonLev


» .

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