Dutasteride Study.

[sam-]

Hair counts during the usage of Avodart:
109.8 for Avodart 2.5 mg/day.

Hair counts after 12 weeks of stopping Avodart:
119.8 for Avodart 2.5 mg/day.

Isn’t that strange. any explanation for that !!! :!: ensativo:

http://www.anagen.net/glaxo3.htm

 

[hairschmair]

Very long half-life?

 

[matt_1_]

Isn't possible that this type of medication takes time before getting out the system?

 

[Cornholio]

VERY long half life for dutasteride... It takes up to 6 months for dutasteride to get out of your system. After 3 month off of dutasteride you still have blood levels of dutasteride, low DHT levels, and therefore may continue to show "improvements" as that study showed. That long half-life is one reason they considered weekly or even monthly dosing of dutasteride (quote from interview with Dr. Sawaya). Of course, that long half life means that if you are the unlucky one who notices sexual dysfunction or perky breasts one day on dutasteride you are going to hate life for a long, long time....

"The terminal half-life of dutasteride is approximately 5 weeks at steady state. The average steady-state serum dutasteride concentration was 40 ng/mL following 0.5 mg/day for 1 year. Following daily dosing, dutasteride serum concentrations achieve 65% of steady-state concentration after 1 month and approximately 90% after 3 months. Due to the long half-life of dutasteride, serum concentrations remain detectable (greater than 0.1 ng/mL) for up to 4 to 6 months after discontinuation of treatment. "

 

[Guest]

This is interesting.

Would there be any benefit in taking finasteride as normal and taking a dose of dutasteride on a monthly basis?

 

[Cornholio]

Dutasteride still requires a therapeutic level in the blood... If it is taken less often than usual (daily) you have to take more to get into the range of proven results. For example instead of .5mg each day 3.5mg each week... or 14 mg monthly... (that isnt proven, im just guestimating). In any case you would have to take the same amount of dutasteride to get comperable effects... The only benefit is less frequent dosing, but the side-effects, risk and cost would be the same. The usual dose .5mg weekly or monthly would probably not add anything to hair loss prevention.

 

[Guest]

I don't really know enough about dutasteride. I haven't really researched it much but due to poor results on the big 3 for coming up to 11months - I am starting to prepare myself for the worst and consider dutasteride in a few months time.

I just think that 98% inhibition of DHT would surely do something nasty to your body in the long run.

 

[Bryan]

Dutasteride still requires a therapeutic level in the blood... If it is taken less often than usual (daily) you have to take more to get into the range of proven results. For example instead of .5mg each day 3.5mg each week... or 14 mg monthly...

EXACTLY!! Some people have the screwball idea that because of the long half-life, taking a single Avodart capsule once a week (for example) is going to be nearly as effective as taking an Avodart capsule every day! But that's completely nutso: you still have to get the same AVERAGE amount of the drug, but the half-life allows you to do that in a very flexible manner. For instance, you could either take 0.5 mg every day, or you could take 3.5 mg once a week, or 7 mg every other week, or 15 mg once a month, etc.

(that isnt proven, im just guestimating). In any case you would have to take the same amount of dutasteride to get comperable effects... The only benefit is less frequent dosing, but the side-effects, risk and cost would be the same. The usual dose .5mg weekly or monthly would probably not add anything to hair loss prevention.

EXACTLY!

Bryan

 

[eliazush]

Hi,

These things aren't backed uo by studies...Not always the serum concnetration reflexs the effect on the body...Plus, Don't forget that 0.5mg is intended to treat the enlargemnet of the prostate gland so I don't see a reason to take dutasteride every day for hairloss, just like finasteride 5mg which may be too high for hairloss but 1mg is fine. So.... I have strated to take dutasteride once a week only ONE capsule. I hope it's enough knowing that its half life is really long AND that the concentration needed for hairloss can be lower than the concentration needed for the prostate.
I dscided to take on capsule a week for these reasons and to minimize side effects as much as possible (such as early aging of the skin, ginomastia, possible CNS effects etc.)

Good luck everyone.

 

[Bryan]

These things aren't backed uo by studies...

WHICH things aren't backed up by studies?? What we've been talking about in this thread HAS been backed up with studies.

Not always the serum concnetration reflexs the effect on the body...

Yes it does. dutasteride's ability to inhibit 5a-reductase is reflected closely by its serum concentration.

So.... I have strated to take dutasteride once a week only ONE capsule. I hope it's enough knowing that its half life is really long AND that the concentration needed for hairloss can be lower than the concentration needed for the prostate.

dutasteride's half-life doesn't have a damned thing to do with it. Also, don't just assume from Merck's marketing decisions (Proscar, Propecia) that less of a drug is "needed" for hair than for the prostate. It's more complicated than that.

Bryan

 

[everysixseconds]

ive been takin 2 capsules of dutasteride (1mg) everyday for the last 5 months and have barely seen results. sure, my hair is mainating and texture has improved. the point im makin is, please dont waste your precious time by takin lower potencies.

 

[ACT10Npack]

Why are people so nervous about taking a daily pill once a day. You need about .5MG of dutasteride to block about 98% of DHT. Which the study was done for FDA approving but stop at phase II. For reason I don't know. Although studies have shown that dutasteride will stay in your system must longer then finasteride, it does not mean you can take 10 times the dose and only take it once a week or once a month. You will not have enough drug in your system to block enough DHT. Which means, you will always shed if your on that way of dose and it increase the sideside over 1000% and/or you could get some severe problems would never happen at the 0.5MG. If I was you and want to take dutasteride, just take the normal dosing. It only takes less then a minute to open the bottle, take the one pill out and get a glass of water and swallow it.

 

[eliazush]

Bryan,

1. Taking dutasteride every day or 3.5mg a week or 14mg every month isn't always the same. Pharmacokinetics is much more complicated than a SIMPLE math. AND it's not backed up...that is, nobody (as far as I know) measured serum levels for patients who took it every day versus patients who took it once week or once a month!

2. Always, there is a threshhold when a medication won't affect...that is, higher serum levels won't always mean higher activity. For examle, if theoretically 0.1mg a day can block ALL 5a-rductase in the body (by the way, nobody talked about half life of this enzyme, which is also important!) then 2mg won't do a thing because all available enzymes are "taken" by the medication. Nobody ever talked about how long the med stays attached to the enzyme. Half life only means how long it take the body to eliminate the entity not how long it works on the site..If it blocks the enzyme forever, till the enzyme is eliminated, more drug consumed won't change a thing!

3. Many details are missing about these issues, so NO ONE, including you, can't claim otherwise. My claims are only theoretical based on knowledge as a pharmacist.

4. I am onl assuming the dosage of dutasteride needed for hairloss should be smaller than for the prsotate, and yes, it IS based on merk studies, which show, BTW, that the connection of efficacy versus serum concentration is niglectable, that is, the difference in activity terms between 5mg of finasteride to 1mg is very small.

5. Merk may have unpure "intentions" to publish what they did, but this is the only scientific literature we all have here, so other any assumption made by you or me whould always stay "assumption". And if merk does have such intentions, why souldn't the creat 2mg for hairloss? The product will be more effective, in your opinion, and will give merk more money because they can claim for more money, because you also get twice as much of finasteride.

6. Hairloss realm is an enigma. More is unknown than known. I wouldn't be as SO "sure" as you are!

 

[Cornholio]

1. Taking dutasteride every day or 3.5mg a week or 14mg every month isn't always the same. Pharmacokinetics is much more complicated than a SIMPLE math. AND it's not backed up...that is, nobody (as far as I know) measured serum levels for patients who took it every day versus patients who took it once week or once a month!

Its not perfect but its close enough to the truth to make a point... you cant take .5mg once a week and expect to get the same serum level or effect as .5mg daily (as the original question suggested). Higher doses less often would be closer to the serum level and effect of the proven .5mg daily dose than .5mg once a week would. The longer half life of dutasteride makes more drug less frequently reasonable but not proven until its proven (of course).

http://ctr.gsk.co.uk/Summary/dutasterid ... IA2004.pdf http://www.regrowth.com/hairloss-remedy ... esults.cfm

The only study with actual information is the phase II avodart study and doses higher than .5mg (2.5mg) daily do actually result in "better" hair counts and lower DHT levels. More drug does affect DHT levels and hair counts. With the .5mg dose of dutasteride there is still room for more 5-AR inhibition... Whether that is worth the cost or risk is another question, but there is a difference.

From the above links (the only information available on hair growth and dutasteride) there is no information allowing a person to assume that less dutasteride would still be superior to finasteride regarding hair. Dutasteride .5mg a day is in fact a near equivalent of finasteride. If you want proven (and equavalent) results at a dose lower than dutasteride .5mg /day just take finasteride.

PS- I do believe that Dutasteride results in lower serum DHT levels than finasteride due to its blockade of the type I and II enzyme, but at the .5mg/day dose there is very little difference in hair growth at 6 months. The benefit of this further supression may be nil, or may manifest at a date beyond the studied 6 months (leap of faith). Also, some people (because of their genetic makeup) may respond better to finasteride or dutasteride... for some one or the other may be better (no way to tell).

The phase II studies do raise a question about the potential benefit of dutasteride doses higher than .5mg/day... Look at the hair counts for 2.5 vs .5mg/day. Whether this difference is significant (small study) or worth the risk is a personal decision and/or awaits further studies (which nobody will pay for, ever, as GSK has given up on this drug). I say this not to encourage anyone to take doses of dutasteride higher than 2.5mg, but just to discribe the real (and only) available studies available on dutasteride.

 

[Bryan]

Although studies have shown that dutasteride will stay in your system must longer then finasteride, it does not mean you can take 10 times the dose and only take it once a week or once a month. You will not have enough drug in your system to block enough DHT.

Baloney. That's EXACTLY what it means. You CAN do it that way, although I personally would draw the line at taking dutasteride at least once a week. That's been examined in a recent very thorough study of dutasteride which I strongly recommend that you read: "A model for the turnover of dihydrotestosterone in the presence of the irreversible 5a-reductase inhibitors GI198745 and finasteride", Gisleskog et al, Clin Pharmacol Ther 1998;64: 636-47. Here's a scan of a set of graphs from that very same study:

http://www.geocities.com/bryan50001/dutasteride2.htm

Look down near the bottom at the graphs in Figure 7. It shows the percentages of DHT reduction from the following doses:

Finasteride: 5 mg/day
Dutasteride: 0.25 mg/day
Dutasteride: 2.5 mg/week
Dutasteride: 10 mg/month

What's fascinating is that with 2.5 mg of dutasteride per week, there is even LESS fluctuation in DHT levels than when you take 5 mg of finasteride every day! :wink:

Bryan

 

[Bryan]

Bryan,

1. Taking dutasteride every day or 3.5mg a week or 14mg every month isn't always the same. Pharmacokinetics is much more complicated than a SIMPLE math. AND it's not backed up...that is, nobody (as far as I know) measured serum levels for patients who took it every day versus patients who took it once week or once a month!

You obviously haven't read and studied the available information on dutasteride. You need to read the following two studies, one of which is the same one I mentioned to "ACT1ONpack" in my post above:

"A model for the turnover of dihydrotestosterone in the presence of the irreversible 5a-reductase inhibitors GI198745 and finasteride", Gisleskog et al, Clin Pharmacol Ther 1998;64: 636-47.

"The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel linear and nonlinear elimination", Gisleskog et al, J Clin Pharmacol 1999; 47, 53-58.

Please see the following graphs from the first study, which show the effects of daily, weekly, and monthly doses of dutasteride:

http://www.geocities.com/bryan50001/dutasteride2.htm

2. Always, there is a threshhold when a medication won't affect...that is, higher serum levels won't always mean higher activity.

Oh, for the love of Christ. How can you say something that silly about dutasteride?? I _guarantee_ you that that dutasteride's activity in inhibiting 5a-reductase is a direct function of its level in the blood serum. Here's another graph from those studies:

http://www.geocities.com/bryan50001/dutasteride4.htm

For examle, if theoretically 0.1mg a day can block ALL 5a-rductase in the body (by the way, nobody talked about half life of this enzyme, which is also important!)

These studies have THOROUGHLY discussed the half-life of the enzyme!! Eliazuh, you're WAY behind the times!

...then 2mg won't do a thing because all available enzymes are "taken" by the medication. Nobody ever talked about how long the med stays attached to the enzyme.

Oh, for crying out loud...even the TITLE of the first study makes reference to the well-known fact that both finasteride and dutasteride are IRREVERSIBLE inhibitors of the type 2 enzyme! That's common knowledge! The meds stay attached PERMANENTLY.

Half life only means how long it take the body to eliminate the entity not how long it works on the site..If it blocks the enzyme forever, till the enzyme is eliminated, more drug consumed won't change a thing!

You're overlooking the fact that even though finasteride and dutasteride are IRREVERSIBLE inhibitors of the type 2 enzyme, MORE of the enzyme is constantly being produced! The amount of DHT in the body is the result of sort of a "balance" between the levels of finasteride or dutasteride, their affinity for the 5a-reductase enzymes, and the production rate of more of that 5a-reductase. It takes LARGE daily doses of dutasteride to really approach 100% inhibition, more than most people would be willing to take. The common doses that are typically used are well below that level, and will produce intermediate results. Raising the typical doses will always result in more and more suppression of DHT.

3. Many details are missing about these issues, so NO ONE, including you, can't claim otherwise. My claims are only theoretical based on knowledge as a pharmacist.

You may be a pharmacist, but you clearly do NOT know very much about dutasteride. Once again, I strongly recommend that you read the studies I cited above.

4. I am onl assuming the dosage of dutasteride needed for hairloss should be smaller than for the prsotate, and yes, it IS based on merk studies, which show, BTW, that the connection of efficacy versus serum concentration is niglectable, that is, the difference in activity terms between 5mg of finasteride to 1mg is very small.

True. It's small, but not ZERO. The same is true for dutasteride: Glaxo's hairloss trial showed better results (haircounts) for larger doses.

5. Merk may have unpure "intentions" to publish what they did, but this is the only scientific literature we all have here, so other any assumption made by you or me whould always stay "assumption". And if merk does have such intentions, why souldn't the creat 2mg for hairloss? The product will be more effective, in your opinion, and will give merk more money because they can claim for more money, because you also get twice as much of finasteride.

They had to draw the line somewhere. It's a reasonable compromise between efficacy and safety.

Bryan

 

[Bryan]

Dutasteride .5mg a day is in fact a near equivalent of finasteride.

Actually, it's a dutasteride dose of 0.1 mg/day which is almost exactly equivalent to finasteride (Proscar), in terms of both serum DHT levels and efficacy in Glaxo's hairloss trial.

Bryan

 

[Cornholio]

Actually, it's a dutasteride dose of 0.1 mg/day which is almost exactly equivalent to finasteride (Proscar), in terms of both serum DHT levels and efficacy in Glaxo's hairloss trial.

Ok, but there isnt a lot of difference between the .5mg/day dutasteride and proscar either in terms of efficacy at 6 months (you yourself have argued that on other forums).

 

[Bryan]

Correct. The difference is fairly modest, especially when you compare the haircounts to the placebo users, which is the proper way to do it. Comparing the haircounts just to the original starting baselines over-inflates the differences a little.

Bryan

 

[eurodane]

Hi,

These things aren't backed uo by studies...Not always the serum concnetration reflexs the effect on the body...Plus, Don't forget that 0.5mg is intended to treat the enlargemnet of the prostate gland so I don't see a reason to take dutasteride every day for hairloss, just like finasteride 5mg which may be too high for hairloss but 1mg is fine. So.... I have strated to take dutasteride once a week only ONE capsule. I hope it's enough knowing that its half life is really long AND that the concentration needed for hairloss can be lower than the concentration needed for the prostate.
I dscided to take on capsule a week for these reasons and to minimize side effects as much as possible (such as early aging of the skin, ginomastia, possible CNS effects etc.)

What are CNS effects if I may ask?

Br

ED