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rooster

11.12.2007, 03:21
 

Topical dutasteride (Topicals & Shampoos)

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..




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Post reply
trojanboy

12.12.2007, 02:40

@ rooster

Topical dutasteride

» 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.



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Post reply
rooster

12.12.2007, 03:36

@ trojanboy

Topical dutasteride

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.




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Post reply
brm

his room,
13.12.2007, 00:06

@ rooster

Topical dutasteride

Did you go thru a major shed after quitting?




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Post reply
abcxyz

13.12.2007, 01:06

@ rooster

Topical dutasteride

» 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.




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---
Rogaine foam + Propecia + Nizoral 1% + Lysine
No longer use topical Dutas as of Nov 2007.


Post reply
Bryan

16.12.2007, 02:33

@ rooster

Topical dutasteride

» 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?

.




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Post reply
rooster

17.12.2007, 03:56

@ Bryan

Topical dutasteride

» » 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.




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Post reply
rooster

17.12.2007, 04:17

@ rooster

Topical dutasteride

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.




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Post reply
Bryan

17.12.2007, 05:48

@ rooster

Topical dutasteride

» » 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:

http://www.geocities.com/bryan50001/graph8.htm

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!

.




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Post reply
Bryan

17.12.2007, 06:00

@ rooster

Topical dutasteride

» 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.

.




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Post reply
Amilcar

17.12.2007, 19:09

@ Bryan

Topical dutasteride

» 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 ?!




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Post reply
Bryan

17.12.2007, 20:36

@ Amilcar

Topical dutasteride

» 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.

.




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Post reply
rooster

17.12.2007, 20:43

@ Bryan

Topical dutasteride

» » 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?




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Post reply
brm

his room,
18.12.2007, 00:57

@ rooster

Topical dutasteride

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.




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email hairsite@aol.com to arrange a meeting.


Post reply
rooster

18.12.2007, 01:46

@ brm

Topical dutasteride

» 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.




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Post reply
brm

his room,
18.12.2007, 04:01

@ rooster

Topical dutasteride

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.




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email hairsite@aol.com to arrange a meeting.


Post reply
boris342002

18.12.2007, 14:31

@ brm

Topical dutasteride

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.
1. 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...?
2. 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?
3. 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.




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Post reply
rooster

18.12.2007, 16:27

@ brm

Topical dutasteride

» 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.




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Post reply
rooster

18.12.2007, 16:30

@ rooster

Topical dutasteride

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)."




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Post reply
brm

his room,
18.12.2007, 17:48

@ rooster

Topical dutasteride

»
» 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.:-) :-)




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email hairsite@aol.com to arrange a meeting.


Post reply
rooster

18.12.2007, 18:10

@ brm

Topical dutasteride

The turnover for the enzyme complex is slow approximately
30 days for the Type II enzyme complex and 14 days for the Type I
complex

The above is why i believe Duta topically once every 5 to 7 days could be very effective.

» »
» » 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.:-) :-)




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


Post reply
brm

his room,
18.12.2007, 22:41

@ rooster

Topical dutasteride

Frankly, I don't know what we can make of this information.
1) a quick turnover in vitro generally points to a quick turnover in vivo. But a slow turnover in vitro doesn't necessarily induce a slow one in vivo
2) Above all, the indication they give is about the HALFLIFE of these complexes. But what do we care? These complexes are the dihydrofinasteride complexes AFTER the chemical reaction, that is, inert products unable to neutralize any other DHT molecule. The only relevant point is the halflife of the reactant: finasteride and dutasteride themselves. And once again, because of this, your point is a good one.




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email hairsite@aol.com to arrange a meeting.


Post reply
Bryan

19.12.2007, 05:18

@ rooster

Topical dutasteride

» So the two questions for me:
»
» How fast would DHT resynthisize in the skin, aka scalp.

After a course of finasteride? I think it's probably about the same as what was shown in that graph I posted previously to be the time required for blood levels of DHT to get back to normal after a dose of finasteride: about 1-2 weeks. It would take even longer after a course of dutasteride, obviously, because of dut's much longer half-life.

» 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 no reason whatsoever to think that the bound enzyme would keep the active duta around the scalp for any extra length of time. As I said before, I think topically-applied dutasteride would be absorbed systemically within minutes, with the exception of a few dut molecules here and there which would be lucky enough to bind to hair follicle enzyme molecules on their way through the skin/scalp. The rest of them would go their merry way into the bloodstream, in my opinion.

.




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


Post reply
Bryan

19.12.2007, 05:45

@ brm

Topical dutasteride

» 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).

You can't possibly have a DHT "upregulation" as long as you keep using a 5a-reductase inhibitor! :-) What you probably meant to say is that the brain's response to 5a-reductase inhibition is to upregulate testosterone production by way of the hypothalamic-pituitary-testicular axis. DHT stays low, but testosterone increases a bit as a response to the lower overall androgenic stimulation.

» 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.

Why on earth would anybody think that an active fin or dut molecule would "hang around" in a tissue?? :-)

» 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)

That seems unlikely in the case of 5a-reductase, because I can show you a study in which RNA levels of 5a-reductase were measured in vitro in human scalp hair follicles, in response to androgenic stimulation. They found that giving testosterone to the hair follicle cultures actually stimulated them to produce MORE 5a-reductase RNA, which is the opposite of what you're suggesting.

» ...or the creation of
» new androgenic receptors locally. Hence the apparent
» loss of efficiency of these drugs after some years.

I think any such upregulations or downregulations as a result of antiandrogens or 5a-reductase inhibitors happen MUCH sooner than a matter of years. I think they start to happen immediately, and are probably complete within days or certainly weeks.

.




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


Post reply
Bryan

19.12.2007, 06:03

@ rooster

Topical dutasteride

» 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.

Keep in mind, though, that that was mainly because most of the 5a-reductase type 2 enzyme had been knocked-out by finasteride. After it's been disabled by an irreversible inhibitor like finasteride or dutasteride, it takes a while for the enzyme to regenerate back to normal levels. DHT is then synthesized much faster when all the 5a-reductase enzyme is fully intact.

.




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


Post reply
Bryan

19.12.2007, 06:23

@ rooster

Topical dutasteride

» As I suspected the enyzme resynthesis is very slow, justifying
» a once a week topical dutatasteride could be very effective.

You still need to demonstrate that a topical dutasteride treatment would have any significant "local" effect at all at inhibiting 5a-reductase, and I don't think you can do that.

.




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


Post reply
Bryan

19.12.2007, 07:05

@ brm

Topical dutasteride

» 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".

The rate at which drugs are eliminated from the body does indeed resemble the rate at which radioactivity decays, for the simple reason that each molecule of the drug is acted upon relatively independently. For example, if each molecule of a given drug floating around in the bloodstream has a 1/2 chance of being "caught", degraded, and excreted by the liver each time that molecule passes around the body, then the total number of those drug molecules in the blood at any given time will indeed drop at a rate that does generally resemble that of radioactive decay.

» 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)

I don't understand what you mean.

» 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.

I don't follow much of what you say in that paragraph, either, but I will say that in the Gisleskog et al studies on dutasteride and finasteride which I have quoted from widely on hairloss sites like this one, slightly over 80% of blood DHT was judged to have come from the type 2 enzyme, while the remainder (slightly less than 20%) was judged to have come from the type 1 enzyme.

» 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.:-) :-)

What do you mean by "reactivity of the endocrine production"? As I pointed out earlier, DHT production remains low as long as you take a 5a-reductase inhibitor. Testosterone synthesis goes up a little, but DHT stays low.

.




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


Post reply
Bryan

19.12.2007, 07:19

@ brm

Topical dutasteride

» Frankly, I don't know what we can make of this information.
» 1) a quick turnover in vitro generally points to a quick turnover in vivo.
» But a slow turnover in vitro doesn't necessarily induce a slow one in vivo

BRM, you have a talent for posting statements which I just can't understand at all! :-)

» 2) Above all, the indication they give is about the HALFLIFE of these
» complexes. But what do we care? These complexes are the dihydrofinasteride
» complexes AFTER the chemical reaction, that is, inert products unable to
» neutralize any other DHT molecule. The only relevant point is the
» halflife of the reactant: finasteride and dutasteride themselves. And once
» again, because of this, your point is a good one.

Who SAYS we care about the half-life of the enzyme/drug complexes?? Obviously, all we do care about is the half-life of the finasteride and dutasteride. I don't understand the point of your paragraph above.

.




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


Post reply
Bryan

19.12.2007, 07:49

@ rooster

Topical dutasteride

» The turnover for the enzyme complex is slow approximately
» 30 days for the Type II enzyme complex and 14 days for the
» Type I complex

I've seen that same estimate, too, and it differs considerably from the numbers reported in the Gisleskog et al studies, which state that the turnover rates for the type 1 and type 2 enzymes (respectively) are 45 and 80 hours.

» The above is why i believe Duta topically once every 5 to 7 days
» could be very effective.

Seriously, don't bet the farm on that! ;-)

.




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


Post reply
Bryan

19.12.2007, 08:19

@ brm

Topical dutasteride

» 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.

How can the "endocrine production of DHT" be just as active as before finasteride intake, once finasteride knocks-out most of the 5a-reductase type 2?

» If your assumption was right, we should see a landing on the curve,
» which we do not see.

Can you explain what you mean by that a little better?

» 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.

I wouldn't say that it's "way steeper".

» It means that the more DHT you inhibit, the more fresh
» dht is rapidly produced.

Nah, I don't think so.

» 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.

Because it only takes about 7 days to recover most (but not all) of the missing DHT.

.




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


Post reply
rooster

19.12.2007, 22:59

@ Bryan

Topical dutasteride

» » 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.
»
» How can the "endocrine production of DHT" be just as active as before
» finasteride intake, once finasteride knocks-out most of the 5a-reductase
» type 2?
»
» » If your assumption was right, we should see a landing on the curve,
» » which we do not see.
»
» Can you explain what you mean by that a little better?
»
» » 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.
»
» I wouldn't say that it's "way steeper".
»
» » It means that the more DHT you inhibit, the more fresh
» » dht is rapidly produced.
»
» Nah, I don't think so.
»
» » 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.
»
» Because it only takes about 7 days to recover most (but not all) of the
» missing DHT.
»
» .

It is clear that Duta doesn't have the effect on scalp DHT compared to circulating DHT (even though it is effective at both, just more on DHT in circulation) This tells me that DUTA is not reaching the scalp and hair follicules as easily. One can ponder why that is, but this is the reason i think a topical duta may be more effective than oral. You know you will be getting the drug into places that oral may not be reaching as easily. I still have a suspicion that the drug may accumulate around the hair follicle for a longer period of time than just minutes as suggested.




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


Post reply
The Rooster

20.12.2007, 00:34

@ rooster

Topical dutasteride

:angry: Get a new name!!I thought you would be polite enough to find another name, but I guess you're not!!




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

---
Four strips from 2001-2007.
3000 FUE scalp/BHT beard grafts from Dr. Umar late June 2008.
(scar repair/hairline softening/crown whirl)


Post reply
Bryan

20.12.2007, 01:26

@ rooster

Topical dutasteride

» It is clear that Duta doesn't have the effect on scalp DHT compared
» to circulating DHT (even though it is effective at both, just more
» on DHT in circulation)

I'm not sure if that's true or not, considering how there are conflicting numbers for levels of scalp/blood DHT reduction reported in different studies which have examined that question. I generally take those reported numbers with a grain or two of salt.

» This tells me that DUTA is not reaching the scalp and hair
» follicules as easily. One can ponder why that is...

Even if the numbers you previously cited for scalp DHT reduction versus blood DHT reduction are correct, I think you may be overlooking a possible simpler explanation for it, which is that it may reflect a much higher level of the type 1 enzyme within scalp skin sections than the type 2 enzyme. Considering how dutasteride is much less potent against type 1 than it is against type 2, that could possibly go a long way toward explaining those numbers, and it doesn't really have anything to do with how easily dutasteride is reaching scalp and hair follicles.

» but this is the reason i
» think a topical duta may be more effective than oral. You know you will be
» getting the drug into places that oral may not be reaching as easily. I
» still have a suspicion that the drug may accumulate around the hair
» follicle for a longer period of time than just minutes as suggested.

I really think that's just wishful thinking.

.




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


Post reply
rooster

25.12.2007, 18:02

@ Bryan

Topical dutasteride

» » So the two questions for me:
» »
» » How fast would DHT resynthisize in the skin, aka scalp.
»
» After a course of finasteride? I think it's probably about the same as
» what was shown in that graph I posted previously to be the time required
» for blood levels of DHT to get back to normal after a dose of finasteride:
» about 1-2 weeks. It would take even longer after a course of dutasteride,
» obviously, because of dut's much longer half-life.
»
» » 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 no reason whatsoever to think that the bound enzyme would keep the
» active duta around the scalp for any extra length of time. As I said
» before, I think topically-applied dutasteride would be absorbed
» systemically within minutes, with the exception of a few dut molecules
» here and there which would be lucky enough to bind to hair follicle enzyme
» molecules on their way through the skin/scalp. The rest of them would go
» their merry way into the bloodstream, in my opinion.
»
» .

Phase 3 for oral duta is happening in Korea. Hopefully we can gleam some good info from the data.




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


Post reply
rooster

27.12.2007, 03:10

@ rooster

Topical dutasteride

» » » So the two questions for me:
» » »
» » » How fast would DHT resynthisize in the skin, aka scalp.
» »
» » After a course of finasteride? I think it's probably about the same as
» » what was shown in that graph I posted previously to be the time
» required
» » for blood levels of DHT to get back to normal after a dose of
» finasteride:
» » about 1-2 weeks. It would take even longer after a course of
» dutasteride,
» » obviously, because of dut's much longer half-life.
» »
» » » 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 no reason whatsoever to think that the bound enzyme would keep
» the
» » active duta around the scalp for any extra length of time. As I said
» » before, I think topically-applied dutasteride would be absorbed
» » systemically within minutes, with the exception of a few dut molecules
» » here and there which would be lucky enough to bind to hair follicle
» enzyme
» » molecules on their way through the skin/scalp. The rest of them would
» go
» » their merry way into the bloodstream, in my opinion.
» »
» » .
»
» Phase 3 for oral duta is happening in Korea. Hopefully we can gleam some
» good info from the data.

Recieved my duta solution today, it is .5MG. I'm going to dillute it down as it appears duta travels through the dermis rather easily.




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


Post reply
HanginInThere

Manila(UwishUrHere),
12.01.2008, 03:51

@ rooster

Topical dutasteride

» » » » So the two questions for me:
» » » »
» » » » How fast would DHT resynthisize in the skin, aka scalp.
» » »
» » » After a course of finasteride? I think it's probably about the same
» as
» » » what was shown in that graph I posted previously to be the time
» » required
» » » for blood levels of DHT to get back to normal after a dose of
» » finasteride:
» » » about 1-2 weeks. It would take even longer after a course of
» » dutasteride,
» » » obviously, because of dut's much longer half-life.
» » »
» » » » 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 no reason whatsoever to think that the bound enzyme would keep
» » the
» » » active duta around the scalp for any extra length of time. As I said
» » » before, I think topically-applied dutasteride would be absorbed
» » » systemically within minutes, with the exception of a few dut
» molecules
» » » here and there which would be lucky enough to bind to hair follicle
» » enzyme
» » » molecules on their way through the skin/scalp. The rest of them
» would
» » go
» » » their merry way into the bloodstream, in my opinion.
» » »
» » » .
» »
» » Phase 3 for oral duta is happening in Korea. Hopefully we can gleam
» some
» » good info from the data.
»
» Recieved my duta solution today, it is .5MG. I'm going to dillute it down
» as it appears duta travels through the dermis rather easily.

seems dute has a reputation for systemic absorbtion
that would scare most guys off




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email hairsite@aol.com to arrange a meeting.

---
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Post reply
rooster

14.01.2008, 03:06

@ Bryan

Topical dutasteride

» » As I suspected the enyzme resynthesis is very slow, justifying
» » a once a week topical dutatasteride could be very effective.
»
» You still need to demonstrate that a topical dutasteride treatment would
» have any significant "local" effect at all at inhibiting 5a-reductase, and
» I don't think you can do that.
»
» .

Bryan, come on you know better than that. Finasteride was going to orifinally be used as a topical. Once the drug comes in contact with the enzyme it binds to it regardless if the drug was administered orally or topically. THIS I DO KNOW.




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


Post reply
boris342002

18.01.2008, 02:38

@ rooster

Topical dutasteride

Rooster,
I have been taking Avodart for over 2 months and I want to take a break from it. Ive been taking 0.5 daily, sometimes 1 a day. How many days or weeks till I will get normal level of DHT as if I never took Avodart?
I am asking this, since I dont want this to occur, I wonder if a week stop could rise DHT level by a whole lot...
Thanks bro!





» » » » So the two questions for me:
» » » »
» » » » How fast would DHT resynthisize in the skin, aka scalp.
» » »
» » » After a course of finasteride? I think it's probably about the same
» as
» » » what was shown in that graph I posted previously to be the time
» » required
» » » for blood levels of DHT to get back to normal after a dose of
» » finasteride:
» » » about 1-2 weeks. It would take even longer after a course of
» » dutasteride,
» » » obviously, because of dut's much longer half-life.
» » »
» » » » 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 no reason whatsoever to think that the bound enzyme would keep
» » the
» » » active duta around the scalp for any extra length of time. As I said
» » » before, I think topically-applied dutasteride would be absorbed
» » » systemically within minutes, with the exception of a few dut
» molecules
» » » here and there which would be lucky enough to bind to hair follicle
» » enzyme
» » » molecules on their way through the skin/scalp. The rest of them
» would
» » go
» » » their merry way into the bloodstream, in my opinion.
» » »
» » » .
» »
» » Phase 3 for oral duta is happening in Korea. Hopefully we can gleam
» some
» » good info from the data.
»
» Recieved my duta solution today, it is .5MG. I'm going to dillute it down
» as it appears duta travels through the dermis rather easily.




boris342002 is located in [NA] and he is available to meet: NO


Post reply
keither

05.06.2013, 08:03

@ boris342002

Topical dutasteride

I crush up dutasteride tablets and add them to my shampoo and it's worked great. Here is where I been buying without a prescription http://instant-online-solution.com




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


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