It seems to me that one could use topical dutasteride once a week with some very good success. Dutasteride will actually bind to the receptor for MONTHS, not days. Once a week could do the trick, maybe once every other week. The molecule is plenty small to penetrace the skin and affect the receptors while hopefully not overdosing to get major systemic sides associated with this drug, i.e. Impotence, depression, high estrogen, brain fog etc…
» It seems to me that one could use topical dutasteride once a week with some
» very good success. Dutasteride will actually bind to the receptor for
» MONTHS, not days. Once a week could do the trick, maybe once every other
» week. The molecule is plenty small to penetrace the skin and affect the
» receptors while hopefully not overdosing to get major systemic sides
» associated with this drug, i.e. Impotence, depression, high estrogen,
» brain fog etc…
are you sure about once a week?
I was on topical dustasteride daily and grew big breasts . got back hair on my temples.
Yes if not every other week. It literally binds to the receptor for over a month. I’m surprised other people aren’t talking about this. Dutasteride on paper should be far superior to finasteride in that it blocks both type one and type two 5 Alpha Reductase. It has a substantially longer half life then Finasteride. I suspect you could get away with once a week no problem. Did you really have some bad sides such as gyno? I got depression on finasteride and quit after many years. Feel MUCH better now.
» » It seems to me that one could use topical dutasteride once a week with
» some
» » very good success. Dutasteride will actually bind to the receptor for
» » MONTHS, not days. Once a week could do the trick, maybe once every
» other
» » week. The molecule is plenty small to penetrace the skin and affect the
» » receptors while hopefully not overdosing to get major systemic sides
» » associated with this drug, i.e. Impotence, depression, high estrogen,
» » brain fog etc…
»
» are you sure about once a week?
»
» I was on topical dustasteride daily and grew big breasts . got back hair
» on my temples.
Did you go thru a major shed after quitting?
» It seems to me that one could use topical dutasteride once a week with some
» very good success. Dutasteride will actually bind to the receptor for
» MONTHS, not days. Once a week could do the trick, maybe once every other
» week. The molecule is plenty small to penetrace the skin and affect the
» receptors while hopefully not overdosing to get major systemic sides
» associated with this drug, i.e. Impotence, depression, high estrogen,
» brain fog etc…
Where did you read that says it will bind to the receptor for months?
I did try top dutas and my hair did feel better or slightly thicker. I stopped about a month ago b/c I ran out of Dutas and it’s too expensive to refill. Maybe I should continue to use it.
» It seems to me that one could use topical dutasteride once a week with some
» very good success. Dutasteride will actually bind to the receptor for
» MONTHS, not days.
You want to use the word “enzyme”, not “receptor”.
So what about the NEW enzyme that starts to form after a day or so?
.
» » It seems to me that one could use topical dutasteride once a week with
» some
» » very good success. Dutasteride will actually bind to the receptor for
» » MONTHS, not days.
»
» You want to use the word “enzyme”, not “receptor”.
»
» So what about the NEW enzyme that starts to form after a day or so?
»
» .
Byran, good question. How long would it take for the enzyme to reappear? The duta should stay in the follicle area for a while, i doubt it would all be systemically absorbed into the body that quickly, but just a guess.
Bryan, on another note i find it interesting that glaxo all of sudden is moving forward with phase 3 trials for alopecia. The data should be interesting, on paper duta should really outperform fina hands down.
Dutasteride in Phase 3 clinical trials for hair loss
Posted on March 7th, 2007 in FDA News, Hair Loss News by admin | 1,347 Views |
GlaxoSmithKline is currently conducting clinical trials for Dutasteride, otherwise known as Avodart, as a treatment for male pattern baldness (MPB).
Dutasteride had been on track for FDA submission as a treatment for Androgenetic Alopecia, but in 2003 Glaxo pulled the plug on their Phase 3 hair loss trials, much to the dismay of many hair loss sufferers worldwide.
Internet rumors persisted for a long time about the reason why Glaxo pulled the plug, but with the release of Avodart as a treatment for Benign Prostatic Hyperplasia (BPH), the drug became readily available to anyone who could obtain a prescription. Since then many men have taken the drug as a hair loss treatment with mixed results. Some men have claimed to have excellent results, while others have complained about increased hair shedding.
The true efficacy will soon be known as it now appears something has changed at Glaxo and the trial is back on. GlaxoSmithKline have set up a Phase 3 clinical study in Korea as part of the process to seek FDA approval for using Dutasteride as a treatment for male pattern hairloss.
A clinical study is being conducted in Korea and is enrolling men of the ages 18 - 49 to test the efficacy of Dutasteride in stimulating hair growth.
Men with a hair loss pattern classified as type IIIv, IV, or V on the modified Norwood-Hamilton classification are eligible to apply, but men who are a type IVa or Va are excluded from the trial.
Other exclusions from the trial include men who:
• Have global scalp hair thinning, including occipital areas
• Have scarring of the scalp or any other condition or disease of the scalp or hair, including diseases of the hair shaft and inability to discontinue use of hair weaving.
• Use hair colorants/hair dyes, or have the remaining traces of colorants in their hair.
• Have used finasteride (Propecia) or other 5 AR inhibitors within the 12 months prior to screening.
• Have previously use of dutasteride.
• Have used phytotherapy (e.g. saw palmetto) within 8 weeks prior to screening.
Or have used any of the following drugs during the 6 months prior to screening:
• Minoxidil (oral or topical)
• Drugs with anti-androgenic properties (e.g., cyproterone acetate, spironolactone, ketoconazole, flutamide, bicalutamide). Cimetidine cannot be used during the study but is not an excluded drug when used during the previous 6 months.
• Topical estrogen, progesterone
• Tamoxifen
• Drugs potentially causing hypertrichosis (e.g., cyclosporine, diazoxide, phenytoin psoralens)
• Anabolic steroids
• Lithium and phenothiazines
The expected total enrollment in this trial is 150 subjects and they will be using 0.5mg of Dutasteride taken daily.
It’s very unlikely that this is the only trial because typically drug trials are done at multiple locations to ensure accuracy. It could either be a pilot trial or Glaxo could possibly be in the midst of setting up more trials at different centers.
» » So what about the NEW enzyme that starts to form after a day or so?
» »
»
» Byran, good question. How long would it take for the enzyme to reappear?
To get a reasonable idea of that, take a look at this often-posted graph from a medical journal study:
It shows actual measured serum DHT levels for up to 7 days in human volunteers who took various SINGLE doses of finasteride. Even though finasteride is pretty much out of the body (or out of the blood, at least) a day or two after the last dose that you take, nevertheless it took up to a week or two for the blood levels of DHT of these test-subjects to get back to normal after those test doses. That’s because the regeneration rate of the type 2 enzyme ITSELF is rather slow. Once finasteride or dutasteride knocks it out, it takes a while for new, “fresh” enzyme to be synthesized within the cell (finasteride and dutasteride are both considered to be irreversible inhibitors of the type 2 enzyme).
» The duta should stay in the follicle area for a while, i doubt it would
» all be systemically absorbed into the body that quickly, but just a guess.
Then I guess that would be the main point of contention here! 
I don’t know of any evidence at all to suggest that dutasteride (or finasteride, for that matter) would hang around for such an incredible amount of time within the confines of a hair follicle, or just in the skin. I think it would last for a matter of MINUTES, not MONTHS!
.
» Bryan, on another note i find it interesting that glaxo all of sudden is
» moving forward with phase 3 trials for alopecia. The data should be
» interesting, on paper duta should really outperform fina hands down.
»
» Dutasteride in Phase 3 clinical trials for hair loss
» Posted on March 7th, 2007 in FDA News, Hair Loss News by admin | 1,347
» Views |
»
» GlaxoSmithKline is currently conducting clinical trials for Dutasteride,
» otherwise known as Avodart, as a treatment for male pattern baldness
» (MPB).
Farrel posted that same information over on HLH several months ago, and I had a big fight with him over that and some related issues.
Frankly, I just don’t buy that story. I’ll believe that Glaxo really did change their mind and decided to pursue Phase 3 clinical trials when I see corroboration for it in other places.
.
» It shows actual measured serum DHT levels for up to 7 days in human
» volunteers who took various SINGLE doses of finasteride. Even though
» finasteride is pretty much out of the body (or out of the blood, at least)
» a day or two after the last dose that you take, nevertheless it took up to
» a week or two for the blood levels of DHT of these test-subjects to get
» back to normal after those test doses. That’s because the regeneration
» rate of the type 2 enzyme ITSELF is rather slow. Once finasteride or
» dutasteride knocks it out, it takes a while for new, “fresh” enzyme to be
» synthesized within the cell (finasteride and dutasteride are both
» considered to be irreversible inhibitors of the type 2 enzyme).
»
Hi,
So Basically you are saying that once you take finasteride and Duta you’ll never have that type 2 enzyme again in your metabolism ?!
» So Basically you are saying that once you take finasteride and Duta
» you’ll never have that type 2 enzyme again in your metabolism ?!
Your question is a little ambiguous, but what I’m saying is that once a molecule of the 5a-reductase type 2 enzyme binds to either finasteride or dutasteride, it’s essentially destroyed as a DHT-producing entity. That individual molecule will no longer be able ever to produce DHT again. Only new, freshly synthesized type 2 molecules that haven’t yet been bound by fin or dut will be able to do that.
.
» » So Basically you are saying that once you take finasteride and Duta
» » you’ll never have that type 2 enzyme again in your metabolism ?!
»
» Your question is a little ambiguous, but what I’m saying is that once a
» molecule of the 5a-reductase type 2 enzyme binds to either finasteride or
» dutasteride, it’s essentially destroyed as a DHT-producing entity. That
» individual molecule will no longer be able ever to produce DHT again.
» Only new, freshly synthesized type 2 molecules that haven’t yet been bound
» by fin or dut will be able to do that.
»
» .
Which leaves us to the real question, how fast does DHT resynthesize? If the enzyme in the skin has bound to duta or fina i really feel the affects could last a week or more, i don’t beleive the drug would disperse in minutes. JUST MY OPINION.
So the two questions for me:
How fast would DHT resynthisize in the skin, aka scalp. Secondly, does the enzyme bound by duta keep the active duta in the area of the scalp for up to a week or does it get systemically absorbed?
I have the feeling that the basical principle of a chemical reaction escapes some of us here. I am no biologist but here’s how I understand the problem. First of all, synthesization of DHT is probably constant throughout the day and throughout life though it follows some peak pattern as does any hormone production. The second point is that hormones abide to a general balance which is controlled by the pituitary gland through the feedback this gland receives in relation with the actual levels of the hormones involved. And the problem with DHT inhibitors is that they disrupt this natural balance (which with us, hairloss sufferers, creates a natural DHT upregulation and therefore a natural hairloss). This seems to explain why the effects both on libido and hairloss are unpredictable from an individual to another. Not to mention the problem of dosage. Last and most of all, we must not forget that once a molecule of fin or dut binds to a molecule of 5ar reductase, this fin or dut molecule is rendered USELESS to neutralize any other 5ar molecule. That’s why this problem of “fin or dut hanging around” is probably pointless. The only problem is the supply rate of dht inibitors for them to be able to counter on a molecular basis (and according to the molecular coefficients the theoretical reaction involves) the relentless and natural production of this damned 5ar reductase. And the problem is, again, all the more difficult to tackle as the disruption of a chemical balance can have any kind of fallout. One of these possible consequences seems to be in many cases an accelerated rate of the production of 5ar reductase (since our system does not understand why the usual amount has suddenly dropped) or the creation of new androgenic receptors locally. Hence the apparent loss of efficiency of these drugs after some years. Many of us know better than me what i am trying to explain here but I think it deserved recalling.
» I have the feeling that the basical principle of a chemical reaction
» escapes some of us here. I am no biologist but here’s how I understand the
» problem. First of all, synthesization of DHT is probably constant
» throughout the day and throughout life though it follows some peak pattern
» as does any hormone production. The second point is that hormones abide to
» a general balance which is controlled by the pituitary gland through the
» feedback this gland receives in relation with the actual levels of the
» hormones involved. And the problem with DHT inhibitors is that they
» disrupt this natural balance (which with us, hairloss sufferers, creates a
» natural DHT upregulation and therefore a natural hairloss). This seems to
» explain why the effects both on libido and hairloss are unpredictable
» from an individual to another. Not to mention the problem of dosage. Last
» and most of all, we must not forget that once a molecule of fin or dut
» binds to a molecule of 5ar reductase, this fin or dut molecule is rendered
» USELESS to neutralize any other 5ar molecule. That’s why this problem of
» “fin or dut hanging around” is probably pointless. The only problem is the
» supply rate of dht inibitors for them to be able to counter on a molecular
» basis (and according to the molecular coefficients the theoretical
» reaction involves) the relentless and natural production of this damned
» 5ar reductase. And the problem is, again, all the more difficult to tackle
» as the disruption of a chemical balance can have any kind of fallout. One
» of these possible consequences seems to be in many cases an accelerated
» rate of the production of 5ar reductase (since our system does not
» understand why the usual amount has suddenly dropped) or the creation of
» new androgenic receptors locally. Hence the apparent loss of efficiency of
» these drugs after some years. Many of us know better than me what i am
» trying to explain here but I think it deserved recalling.
Bryan posted an excerpt earlier that demostrates that even though finasterdide is out of the body completely the levels of DHT stays low for some time. This should mean that DHT is not synthasized rapidly, but over many days.
No. I believe we are confusing the LEVEL and the PRODUCTION RATE. If you pay attention to these graphs posted by Bryan, they show that the serum level is divided by 1.5, 2 or 3. This is a lot. Whereas the finasteride has become inactive after a few hours, maybe because of its quite short half life and above all because it has been chemically consumed to neutralize DHT molecules, the endocrine production of DHT (which I believe is at least as active as before the finasteride intake), is simply insufficient to get this level to its previous value within, say, a day or two. If your assumption was right, we should see a landing on the curve, which we do not see. What’s more if you look closely at the curves, you can see how the average slope is way steeper for higher finasteride concentrations, which explains why all curves get near one to the other after 7 days. It means that the more DHT you inhibit, the more fresh dht is rapidly produced. If not, explain to me how the 5mg finasteride could be in the vicinity of the 0.2 or 0.04 mg after 7 days whereas the DHT was way more severely suppressed in the first place.
Hi guys,
I usually hang around on the HT section but its good to pop in here once in a while. I had some questions for all of you.
- How do you apply the topical dutasteride? Do you take the avodart pill, split it and apply the gel like content on your scalp? If so, where, what if you are a type 5A…?
- What if you dont swallow the avodart capsule, but rather leave it in your mouth till it dissolves, anyone tried it (it tastes like crap) but do you think it can loose its effect as opposed to swallowing the pill?
- Im curious why on the glaxo trial, they would leave out the type5A? any ideas?
Cheers,
» No. I believe we are confusing the LEVEL and the PRODUCTION RATE. If you
» pay attention to these graphs posted by Bryan, they show that the serum
» level is divided by 1.5, 2 or 3. This is a lot. Whereas the finasteride
» has become inactive after a few hours, maybe because of its quite short
» half life and above all because it has been chemically consumed to
» neutralize DHT molecules, the endocrine production of DHT (which I
» believe is at least as active as before the finasteride intake), is simply
» insufficient to get this level to its previous value within, say, a day or
» two. If your assumption was right, we should see a landing on the curve,
» which we do not see. What’s more if you look closely at the curves, you
» can see how the average slope is way steeper for higher finasteride
» concentrations, which explains why all curves get near one to the other
» after 7 days. It means that the more DHT you inhibit, the more fresh
» dht is rapidly produced. If not, explain to me how the 5mg finasteride
» could be in the vicinity of the 0.2 or 0.04 mg after 7 days whereas the
» DHT was way more severely suppressed in the first place.
» No. I believe we are confusing the LEVEL and the PRODUCTION RATE. If you
» pay attention to these graphs posted by Bryan, they show that the serum
» level is divided by 1.5, 2 or 3. This is a lot. Whereas the finasteride
» has become inactive after a few hours, maybe because of its quite short
» half life and above all because it has been chemically consumed to
» neutralize DHT molecules, the endocrine production of DHT (which I
» believe is at least as active as before the finasteride intake), is simply
» insufficient to get this level to its previous value within, say, a day or
» two. If your assumption was right, we should see a landing on the curve,
» which we do not see. What’s more if you look closely at the curves, you
» can see how the average slope is way steeper for higher finasteride
» concentrations, which explains why all curves get near one to the other
» after 7 days. It means that the more DHT you inhibit, the more fresh
» dht is rapidly produced. If not, explain to me how the 5mg finasteride
» could be in the vicinity of the 0.2 or 0.04 mg after 7 days whereas the
» DHT was way more severely suppressed in the first place.
Scalp DHT suppression, which is felt to be correlated to a drug’s effectiveness, was measured and showed that finasteride decreased scalp DHT by 32%, dutasteride 0.5 mg by 51% and dutasteride 2.5 mg showed 79% suppression. DHT concentration in the blood was decreased 73% by finasteride, 92% by dutasteride 0.5mg. and 96% by dutasteride 2.5 mg . The speed by which drugs are eliminated from the body are measured by a value which is called “half-life”. The half-life of finasteride is six to eight hours whereas for dutasteride it is four to five weeks, which means that when one stops taking dutasteride, it will take several months before the drug is out of the system. When blood DHT was measured in these patients 12 weeks after stopping the medication, the finasteride treated patients had a normal DHT level while the dutasteride 0.5 still showed a 10% decrease and the dutasteride 2.5 mg treated patients still had significantly lowered DHT levels.
As I suspected the enyzme resynthesis is very slow, justifying a once a week topical dutatasteride could be very effective. Also, I has some beleif that topical duta may be superior to oral.
in vitro binding studies examining the potential
of finasteride to inhibit either isozyme revealed a 100-fold
selectivity for the human Type II 5a-reductase over Type I isozyme
(IC50=500 and 4.2 nM for Type I and II, respectively). For both
isozymes, the inhibition by finasteride is accompanied by reduction of
the inhibitor to dihydrofinasteride and adduct formation with NADP+.
The turnover for the enzyme complex is slow ([half-life] approximately
30 days for the Type II enzyme complex and 14 days for the Type I
complex)."
»
» Scalp DHT suppression, which is felt to be correlated to a drug’s
» effectiveness, was measured and showed that finasteride decreased scalp
» DHT by 32%, dutasteride 0.5 mg by 51% and dutasteride 2.5 mg showed 79%
» suppression. DHT concentration in the blood was decreased 73% by
» finasteride, 92% by dutasteride 0.5mg. and 96% by dutasteride 2.5 mg . The
» speed by which drugs are eliminated from the body are measured by a value
» which is called “half-life”. The half-life of finasteride is six to eight
» hours whereas for dutasteride it is four to five weeks, which means that
» when one stops taking dutasteride, it will take several months before the
» drug is out of the system. When blood DHT was measured in these patients
» 12 weeks after stopping the medication, the finasteride treated patients
» had a normal DHT level while the dutasteride 0.5 still showed a 10%
» decrease and the dutasteride 2.5 mg treated patients still had
» significantly lowered DHT levels.
Regarding dutasteride, we do not have the relevant charts. Maybe someone can post them, I don’t know. You say that “The
speed by which drugs are eliminated from the body are measured by a value which is called “half-life””. I don’t believe this is true. Halflife is a commonly used parameter in radioactivity to characterize the time needed for the activity of the product to be half what it is at t=0. The speed with which the drug is eliminated from the body would rather be the “excretion time”. If Iremember correctly, dut’s halflife is indeed around 5 weeks and dut’s excretion time around 9 months. Well, never mind anyway since this does not answer our question. Nor does your post either. The harsh effect of dut just renders the “recovery time” even longer. Two more elements should be considered:1) we do not know whether dutasteride doesn’t induce a phenomenon of hysteresis (a severe disruption of the basical recovery process) 2) Above all we have no indication as to the nature of this DHT blood serum measured in these indivduals (to say nothing about the evolution of their hairloss during these “recovery” months). That is, the recovery rate of DHT type 2 might be way higher than type 1’s. That would explain why the overall DHT concentration remains low in dut’s case. I really do believe this since I have more or less experienced it in my own case: having bloodtests carried out regurlarly, I managed to conclude that a high DHT blood serum level was far from being infallibly related to a severe hairloss in the 1 to 4 months following. The only explanation could be that the most harmful DHT type (2) was relatively lower than the type 1. But as to this last hypothesis, I may be completely wrong. I do not know whether DHT can be broken down into variable ratios of type 1 and type 2.
Finally, I would like to stress that we do in fact agree because whatever the situation following the intake of a single dose of DhT inhibitors, it takes some time for the dht level to reach its previous level. So it means anyway that hairloss HAS to remain relatively low in the wake. The point of contention is the reactivity of the endocrine production. You think it is weak. I think it is strong. But since the halflife of dut is way higher than fin’s, your experiment is worth trying.