MDF topical from Samson Therapeutics

Topicals for hair loss
41

» Bryan,
»
» In studies directly comparing spironolactone and flutamide,flutamide has
» been shown to be a more potent antiandrogen (Moghetti, P: J. Clin.
» Endocrinol. Metab. 85(1) 2000).

I acknowledge that flutamide is a generally more powerful antiandrogen than spironolactone, at least at the doses of both drugs which are typically used. But spironolactone does have one PROFOUND advantage over flutamide: it has at least a modest “local” antiandrogenic effect when applied topically, but flutamide doesn’t have any at all.

If you were a virile young male who is concerned about the possibility of developing nasty sexual side effects, which drug would YOU choose to use: topical spiro, which has virtually ZERO chance of systemic absorption (although its “local” effect is only mild-to-moderate), or topical flutamide, which has no “local” effect at all (according to the animal studies), and whose antiandrogenic effects come about EXCLUSIVELY by way of systemic absorption? :slight_smile:

Again I point out that if topical flutamide has no “local” antiandrogenic effect at all, there’s really no particular reason to use it topically in the first place. It would be a lot simpler and far less messy just to SWALLOW a proper dose of the drug.

» But more importantly from a practical
» perspective, spironolactone has an objectionable odor especially when
» combined with minoxdil and requires a viscid base to remain stable in
» solution. This imposes a dilemma on patients: they must either tolerate
» the odor or messyness (most do not) or separate the spironolatone
» application from the minoxidil application–a ritual that quickly becomes
» too bothersome for the patient, who eventually looks for another type of
» treatment.

Dr. Proctor says he’s developed a way to keep spironolactone and minoxidil stabilized when used together. He uses that technique in Proxiphen (which, BTW, has no objectionable odor). That would appear to make a choice of topical spironolactone easily preferable to topical flutamide, especially considering the other points I’ve made about the lack of a “local” effect with flutamide.

» RU58841 is a wonderful drug that will never see the light of day because
» of the disinterest of Roussel Uclaf (now a part of Aventis) to pursue the
» expense of an FDA approval. (Compounders don’t need an FDA approval for
» hair loss, but we are legally bound to use components that are FDA approved
» for some legitimate indication.)

Considering that there’s no Federal law (yet) establishing RU58841 as a prescription drug, I can’t help but question the accuracy of your claim that you would be “legally” prohibited from using RU58841, assuming that you obtained a license to use it from the company that owns the rights (see the other nearby comment from another poster about this same issue).

» Bryan, of course we looked at alternatives that you consider worthy,
» and there is a reason why we rejected them.

I think you should go back and and reconsider those reasons, taking into account what I’ve said in this thread.

.

42

» It is important for people considering the use of MDF or other
» flutamide-containing compounds to look at your experience (and ours)
» and to have some skepticism about the hysterics that abound on this forum
» about flutamide.

In view of the animal studies, I think skepticism about topical flutamide itself is entirely justified. Don’t you agree?

» Another point I should mention is that, when using a topical
» agent, you can also restrict the amount and coverage to just the
» most severe areas of hairloss–this is a form of dose control that
» you do not have with an oral agent.

Again I ask you: if a topical agent has no “local” effect at all where it’s applied, then what even is the purpose of applying it topically in the first place? Why not just swallow it, and save yourself a lot of trouble?

.

43

» » Bryan,
» »
» » In studies directly comparing spironolactone and flutamide,flutamide
» has
» » been shown to be a more potent antiandrogen (Moghetti, P: J. Clin.
» » Endocrinol. Metab. 85(1) 2000).
»
» I acknowledge that flutamide is a generally more powerful antiandrogen
» than spironolactone, at least at the doses of both drugs which are
» typically used. But spironolactone does have one PROFOUND advantage
» over flutamide: it has at least a modest “local” antiandrogenic effect
» when applied topically, but flutamide doesn’t have any at all.
»
» If you were a virile young male who is concerned about the possibility of
» developing nasty sexual side effects, which drug would YOU choose to use:
» topical spiro, which has virtually ZERO chance of systemic absorption
» (although its “local” effect is only mild-to-moderate), or topical
» flutamide, which has no “local” effect at all (according to the animal
» studies), and whose antiandrogenic effects come about EXCLUSIVELY by way of
» systemic absorption? :slight_smile:
»
» Again I point out that if topical flutamide has no “local” antiandrogenic
» effect at all, there’s really no particular reason to use it topically in
» the first place. It would be a lot simpler and far less messy just to
» SWALLOW a proper dose of the drug.
»
» » But more importantly from a practical
» » perspective, spironolactone has an objectionable odor especially when
» » combined with minoxdil and requires a viscid base to remain stable in
» » solution. This imposes a dilemma on patients: they must either
» tolerate
» » the odor or messyness (most do not) or separate the spironolatone
» » application from the minoxidil application–a ritual that quickly
» becomes
» » too bothersome for the patient, who eventually looks for another type
» of
» » treatment.
»
» Dr. Proctor says he’s developed a way to keep spironolactone and minoxidil
» stabilized when used together. He uses that technique in Proxiphen (which,
» BTW, has no objectionable odor). That would appear to make a choice of
» topical spironolactone easily preferable to topical flutamide, especially
» considering the other points I’ve made about the lack of a “local” effect
» with flutamide.
»
» » RU58841 is a wonderful drug that will never see the light of day
» because
» » of the disinterest of Roussel Uclaf (now a part of Aventis) to pursue
» the
» » expense of an FDA approval. (Compounders don’t need an FDA approval
» for
» » hair loss, but we are legally bound to use components that are FDA
» approved
» » for some legitimate indication.)
»
» Considering that there’s no Federal law (yet) establishing RU58841 as a
» prescription drug, I can’t help but question the accuracy of your claim
» that you would be “legally” prohibited from using RU58841, assuming that
» you obtained a license to use it from the company that owns the rights (see
» the other nearby comment from another poster about this same issue).
»
» » Bryan, of course we looked at alternatives that you consider worthy,
» » and there is a reason why we rejected them.
»
» I think you should go back and and reconsider those reasons, taking into
» account what I’ve said in this thread.
»
»

Bryan,

I’m sorry that my business travels will make my contributions a bit spotty on this forum, but let me say that we, indeed, are looking at licensing and other co-partnering arrangements in the future (I cannot say when or with whom at this time.) But these licensing opportunities all come with obligations. In particular, they require financial reserves and performance guarantees that, as a startup company, we will need to earn first with the sales of MDF.

I should mention that this is more than just an business interest of mine, since I have been using MDF longer than any other patient, and I would want to have available a treatment that is equipotent to flutamide that has fewer side effects. Unfortunately, like many other users of antiandrogens (and I have been treated with many of the antiandrogens commonly available in the U.S. over the past 28 years), I have found that they gradually lose their effectiveness over time. To date, from my experience, only flutamide has had the potency to significantly regrow hair–and to retain that hair–after many years of continuous use in a patient. So our interest in providing any improved hair loss treatment without flutamide must focus on retaining this potency level while reducing or eliminating systemic absorption and the attendant side effects.

RonLev

44

1: Int J Pharm. 2000 Jan 20;194(1):125-34. Links
New topical antiandrogenic formulations can stimulate hair growth in human bald scalp grafted onto mice.Sintov A, Serafimovich S, Gilhar A.
Ben-Gurion University of the Negev, The Institutes for Applied Research, PO Box 653, Beer-Sheva, Israel. asintov@bgumail.bgu.ac.il

The purpose of this study was to test the ability of topical formulations of finasteride and flutamide to re-enlarge hair follicles in male-pattern baldness. This was evaluated by an experimental model of human scalp skin graft transplanted onto SCID mice. A comparison was made between formulations containing finasteride and flutamide, and a vehicle formulation in terms of the mean hairs per graft, length, diameter of the shafts, and structures of the growth stages of the hair. Flutamide and finasteride had a significantly higher effect (P<0.05) than the placebo in all the tested parameters, but flutamide demonstrated more hair per graft and longer hair shafts than finasteride (P<0.05). The number of hairs per graft for flutamide and finasteride groups were 1.22+/-0. 47 and 0.88+/-0.95 hairs/0.5 mm2 graft, respectively, versus 0. 35+/-0.6 hairs/graft for vehicle-treated graft. Similarly, hair lengths for flutamide and finasteride were 5.82+/-0.50 and 4.50+/-0. 32 mm, respectively, versus 2.83+/-0.18 mm for the vehicle-treated grafts. An in vitro diffusion study of flutamide gel using hairless mouse skin demonstrated the beneficial effect of the vehicle composition in comparison with a hydroalcoholic solution or a gel containing no penetration enhancer. It is therefore suggested that this topical composition containing flutamide or finasteride may effectively result in regression of male-pattern baldness

If only one didn’t get nausea, diarreaha, no erections, no sex drive from it…and no energy either, dont forget that.

45

» It is therefore suggested that this topical composition containing
» flutamide or finasteride may effectively result in regression of
» male-pattern baldness

Would it really reverse baldness? That’s a bold claim

46

» » It is therefore suggested that this topical composition containing
» » flutamide or finasteride may effectively result in regression of
» » male-pattern baldness
»
» Would it really reverse baldness? That’s a bold claim

I think what is meant by “reverse the regression” in this instance is a stoppage of further regression. And it probably does as transexual’s who get on flutamide usually dont lose any more hair after getting on it. At first glance, a topical flutamide that could be liposomally or nanosomally delivered would seem a great idea, but I think I remeber reading it has to be metabolized to hydroxyflutamide or somthing similar to actually block the human androgen receptor----I could be wrong about that its been a long time since I read any of that stuff.

47

Hey Benji, you wrote earlier that you used topical flutamide before and got libido issues after just 3 days. What product was that exactly ? what was the concentration of flutamide ?

El Duterino

48

» I should mention that this is more than just an business interest of mine,
» since I have been using MDF longer than any other patient, and I would want
» to have available a treatment that is equipotent to flutamide that has
» fewer side effects.

I notice that in your replies to me, you always quote my entire post without bothering to actually ANSWER any of the direct questions that I pose to you. Maybe you could start doing that now? :slight_smile:

What is your response to the central point that I’ve been making in this entire thread, which is that the animal studies (with the single exception of the Sintov study) show that there is no “local” effect from the topical application of flutamide, and that the observable antiandrogenic effect comes exclusively from the systemic absorption of the drug? Do you acknowledge and accept that scientific evidence, or do you deny it? If you accept it, why don’t you recommend that people simply swallow the correct dose of flutamide, instead of applying it topically? If you deny it, then how do you explain the results of the scientific studies?

.

49

I’m still waiting for the Proctor studies on his product that grows significantly more hair than any other agent out there. :hungry:

50

» I’m still waiting for the Proctor studies on his product that grows
» significantly more hair than any other agent out there. :hungry:

RonLev can’t really give a similar response; that is to say, he can’t simply claim that he’s observed the hair-growing effects of his topical flutamide product in humans, just like what Dr. Proctor has said about Proxiphen. That’s because that explanation STILL doesn’t address the likelihood that it was due to the systemic absorption of the drug, and not a “local” effect.

.

51

» » I’m still waiting for the Proctor studies on his product that grows
» » significantly more hair than any other agent out there. :hungry:
»
» RonLev can’t really give a similar response; that is to say, he can’t
» simply claim that he’s observed the hair-growing effects of his topical
» flutamide product in humans, just like what Dr. Proctor has said about
» Proxiphen. That’s because that explanation STILL doesn’t address the
» likelihood that it was due to the systemic absorption of the drug, and not
» a “local” effect.
»
» .

I’m referring to the claims of the product when it comes to results. Maybe Ron has something similar on his website…I didn’t see it.

I have no desire to use flutamide btw…although I’ve always said if there’s something out there that works wonders I’d consider it. Maybe. Possibly.
I don’t know if Ron is saying there is no systemic absorption(it seems he said there is some), but I wonder if the below would be a good candidate for limiting or even preventing that problem, and therefore settling this once and for all- if topical flutamide works via a “local” effect. Or is he already using something like this…

"Salvona Technologies has launched a technology platform that can be used to encapsulate a wide range of functional ingredients. SalSphere is based on submicron spheres with average diameters of 100–300 nm. This size makes them too large to be considered nanotechnology under the new FDA regulations. The technology is made from botanical ingredients and is suitable for topical applications to meet the growing demand for increased performance in skin and hair care products. The new platform is an extension of Salvona’s NanoSal technology platform.
This new technology platform is recommended for water-based applications. The spheres adhere to the skin as a result of their lipophilic properties and electrostatic forces. The platform can be used to encapsulate a wide range of functional ingredients including antiaging, sun filters and dermatological actives.

The company reports the platform is not able to penetrate the stratum corneum but rather deposits on top of skin to form a reservoir from which the encapsulated ingredient can slowly be released. This technology enhances efficacy and reduces skin irritation. The release mechanism of actives from the platform is based on five factors including: natural diffusion triggered by mechanical effects such as rubbing; exposure to heat; partition of the spheres into the lipid intercellular layer of the skin; and endogenous enzymatic activity such as lipase that exhibits elevated activity in areas of inflammation."

52

» I’m referring to the claims of the product when it comes to results.

I don’t doubt that flutamide can be effective at fighting MPB, if a sufficient quantity is used. The only real question that remains up in the air is whether or not it can be used SAFELY as well as effectively, as in free of side effects.

» I have no desire to use flutamide btw…although I’ve always said if
» there’s something out there that works wonders I’d consider it. Maybe.
» Possibly.
» I don’t know if Ron is saying there is no systemic absorption(it seems
» he said there is some),

At one point he did come right out and admit that it worked systemcially, which to me was a rather shocking admission.

» but I wonder if the below would be a good candidate for limiting
» or even preventing that problem, and therefore settling this
» once and for all- if topical flutamide works via a “local” effect.
» Or is he already using something like this…
»
»
» “Salvona Technologies has launched a technology platform that can be used
» to encapsulate a wide range of functional ingredients…”

Jacob, can you think of any reason why such a thing as they describe there would enable topical flutamide to have a “local” effect?

.

53

» »
» »
» » “Salvona Technologies has launched a technology platform that can be
» used
» » to encapsulate a wide range of functional ingredients…”
»
» Jacob, can you think of any reason why such a thing as they describe there
» would enable topical flutamide to have a “local” effect?
»
» .

Yep.

54

» » Jacob, can you think of any reason why such a thing as
» » they describe there would enable topical flutamide
» » to have a “local” effect?
»
» Yep.

Good.

55

» » » Jacob, can you think of any reason why such a thing as
» » » they describe there would enable topical flutamide
» » » to have a “local” effect?
» »
» » Yep.
»
» Good.

Bryan,

I don’t think our recent exchanges have really changed my position or yours, so I haven’t responded to some of these replies. My position, as I have stated, is that flutamide has shown a greater effectiveness (and a greater duration of effectiveness over several years of use, which is just as important) in regrowing and/or retaining hair, at the expense of some systemic absorption and consequently some side effects, which vary from one individual patient to another. Your focus on one (animal) study simply confirms that flutamide’s effects can be systemic, they do not preclude that their effects can also be local, especially when doses are titrated–NO STUDY HAS BEEN PUBLISHED TO DENY OR CONFIRM THIS (and unfortunately most clinical practitioners have to depend on their empirical judgment, in the absence of studies that would resolve this question that pharma refuses to fund.) I don’t think we need to belabor our differences in opinion. That is where my position stands, and it is not disputed by our dermatologic consultants. Naturally, I would like a “perfect” antiandrogen that has the effectiveness of flutamide but without any systemic effects, but we do not have such an agent yet. When you are presented with a patient in dispair over hairloss who does not respond well to lower-potency treatments, we need to offer a solution, albiet with fully disclosing to the patient that there are risks and benefits, as with any other treatment. Bryan, have you ever been faced with accepting or rejecting a treatment that your doctor considered justified after he duly advised you of possible side effects? This is a fact of life in every day clinical practice.

RonLev

56

» Hey Benji, you wrote earlier that you used topical flutamide before and got
» libido issues after just 3 days. What product was that exactly ? what was
» the concentration of flutamide ?
»
» El Duterino

It was a few years ago. It was the 2% flutamide gel from lipoxidil

they dont sell it anymore I think, last I checked lipoxidil didn’t sell much at all anymore

57

» » Hey Benji, you wrote earlier that you used topical flutamide before and
» got
» » libido issues after just 3 days. What product was that exactly ? what
» was
» » the concentration of flutamide ?
» »
» » El Duterino
»
»
»
» It was a few years ago. It was the 2% flutamide gel from lipoxidil
»
» they dont sell it anymore I think, last I checked lipoxidil didn’t sell
» much at all anymore

Ok. I use SINERE Flutagel at 1%, that special gel has been formulated to minimize systemic absorbtion and maximize local effects. Highly recommended for a pin-point boost at the hairline if you are already on a DHT inhibitor.

58

» Bryan,
»
» I don’t think our recent exchanges have really changed my position or
» yours, so I haven’t responded to some of these replies. My position, as
» I have stated, is that flutamide has shown a greater effectiveness (and a
» greater duration of effectiveness over several years of use, which is just
» as important) in regrowing and/or retaining hair, at the expense of some
» systemic absorption and consequently some side effects, which vary from
» one individual patient to another.

What I’ve tried to understand about your position is how you explain the contrary results of most of the animal experiments with topical flutamide. Trying to draw that information out of you has been quite a formidable task, especially when you won’t answer specific questions. I assure you that my questions aren’t at all rhetorical, they are there for a very specific purpose, and they are very deliberate.

» Your focus on one (animal) study…

There are THREE animal studies that I’m aware of which tested topical flutamide in animals (rodents). The latest one is the Sintov study, with which I’m sure you are already quite familiar. The two earlier studies are the ones I cited in an earlier post. The Chen et al study clearly demonstrated a TOTAL lack of any “local” effect whatsoever. The other remaining one from 1975 had rather similar results as Chen et al.

» …simply confirms that
» flutamide’s effects can be systemic, they do not preclude
» that their effects can also be local, especially when doses are
» titrated–NO STUDY HAS BEEN PUBLISHED TO DENY OR CONFIRM THIS

But I’ve already explained to you that the Chen et al study does show a complete absence of any local effect, including when the dose is titrated to lower levels. You can clearly see that in the graph that I posted for you, from that study.

Do you understand now why I’m complaining about your lack of responsiveness to everything I’ve been posting? If you found fault with the scientific evidence that I’ve been presenting, why are you only NOW apparently denying the powerful evidence of the Chen et al study? Why didn’t you do that way back when I first posted it?

» I don’t think we need to belabor our differences
» in opinion. That is where my position stands, and
» it is not disputed by our dermatologic consultants.

I’d be satisfied just to KNOW exactly what your position is! :wink:

Do you or do you not believe the results of the Chen et al study, and the other one from 1975? If you believe and accept them, then what is your rationale for thinking that your new MDF product can be useful for humans? Do you believe that your product has a “local” effect, despite the findings of those earlier studies? If so, WHY do you believe that? Do you believe that the rodents used in those earlier studies absorb topical flutamide in some way, shape, or fashion which precludes them from having a “local” effect, as opposed to what happens when it’s used in humans? Or do you believe that the specialized vehicle that you’re using in your product accounts for the difference? I just want you to TELL ME WHAT YOU BELIEVE, and don’t leave me guessing! :slight_smile:

» Bryan, have you ever been faced with accepting or rejecting
» a treatment that your doctor considered justified after he duly
» advised you of possible side effects?

No, that hasn’t happened to me yet (see how I’m careful to answer YOUR questions? ;-)).

.

59

» » Bryan,
» »
» » I don’t think our recent exchanges have really changed my position or
» » yours, so I haven’t responded to some of these replies. My position,
» as
» » I have stated, is that flutamide has shown a greater effectiveness (and
» a
» » greater duration of effectiveness over several years of use, which is
» just
» » as important) in regrowing and/or retaining hair, at the expense of
» some
» » systemic absorption and consequently some side effects, which vary from
» » one individual patient to another.
»
» What I’ve tried to understand about your position is how you explain the
» contrary results of most of the animal experiments with topical flutamide.
» Trying to draw that information out of you has been quite a formidable
» task, especially when you won’t answer specific questions. I assure you
» that my questions aren’t at all rhetorical, they are there for a
» very specific purpose, and they are very deliberate.
»
» » Your focus on one (animal) study…
»
» There are THREE animal studies that I’m aware of which tested topical
» flutamide in animals (rodents). The latest one is the Sintov study, with
» which I’m sure you are already quite familiar. The two earlier studies are
» the ones I cited in an earlier post. The Chen et al study clearly
» demonstrated a TOTAL lack of any “local” effect whatsoever. The other
» remaining one from 1975 had rather similar results as Chen et al.
»
» » …simply confirms that
» » flutamide’s effects can be systemic, they do not preclude
» » that their effects can also be local, especially when doses are
» » titrated–NO STUDY HAS BEEN PUBLISHED TO DENY OR CONFIRM THIS
»
» But I’ve already explained to you that the Chen et al study does
» show a complete absence of any local effect, including when the dose is
» titrated to lower levels. You can clearly see that in the graph that I
» posted for you, from that study.
»
» Do you understand now why I’m complaining about your lack of
» responsiveness to everything I’ve been posting? If you found fault with
» the scientific evidence that I’ve been presenting, why are you only NOW
» apparently denying the powerful evidence of the Chen et al study?
» Why didn’t you do that way back when I first posted it?
»
» » I don’t think we need to belabor our differences
» » in opinion. That is where my position stands, and
» » it is not disputed by our dermatologic consultants.
»
» I’d be satisfied just to KNOW exactly what your position is! :wink:
»
» Do you or do you not believe the results of the Chen et al study,
» and the other one from 1975? If you believe and accept them, then what is
» your rationale for thinking that your new MDF product can be useful for
» humans? Do you believe that your product has a “local” effect, despite the
» findings of those earlier studies? If so, WHY do you believe that? Do you
» believe that the rodents used in those earlier studies absorb topical
» flutamide in some way, shape, or fashion which precludes them from having a
» “local” effect, as opposed to what happens when it’s used in humans? Or do
» you believe that the specialized vehicle that you’re using in your
» product accounts for the difference? I just want you to TELL ME WHAT YOU
» BELIEVE, and don’t leave me guessing! :slight_smile:
»
» » Bryan, have you ever been faced with accepting or rejecting
» » a treatment that your doctor considered justified after he duly
» » advised you of possible side effects?
»
» No, that hasn’t happened to me yet (see how I’m careful to answer YOUR
» questions? ;-)).
»
»
Bryan,

You are erecting a very aggressive rebuttal on a slim scientific foundation. The Chen studies (1995) were all done in hamsters. Sintov (2000) tried to resolve that problem by testing the topical effect of flutamide on human bald skin grafted onto mice–the closest biological model one can use to approximate the actual clinical use of flutamide in humans, given that using actual patients was far too expensive for his group to fund; and he did come to the conclusions that we stated.

How about giving this contentious debate a rest? The only proof that matters is clinical evidence. I will post a new thread shortly that will ask patients who are already using a flutamide (or flutamide congener)-containing topical treatment to express their views on effectiveness and side effects. To my knowledge, there are 4 such preparations on the market–either in the U.S. or in Europe–and it would be better for the people who have more than an academic interest to participate in this discussion.

RonLev

60

» Bryan,
»
» You are erecting a very aggressive rebuttal on a slim scientific
» foundation. The Chen studies (1995) were all done in hamsters. Sintov
» (2000) tried to resolve that problem by testing the topical effect of
» flutamide on human bald skin grafted onto mice–the closest biological
» model one can use to approximate the actual clinical use of flutamide in
» humans…

The closest biological model to humans was to test it on MICE with Severe Combined Immune Deficiency? That’s a big improvement over normal hamsters?? :slight_smile:

» How about giving this contentious debate a rest?

Yes, let’s give it a rest. I’m satisfied that I’ve thoroughly made my point, even if I haven’t gotten much in the way of specific answers from you. I’m going to assume that you simply don’t KNOW the answers to the specific questions I’ve posed to you, and/or you don’t care to speculate about them. All you really had to do from the very start was just tell me that you couldn’t/wouldn’t answer them. But I’m (reasonably) satisfied now that I did the best I could do, so let’s drop it…

.