2 Dutas a week?

[dut]

Whoa dutasteride! Maybe I've always read Bryan's chart incorrectly but with the shorter half-life of dutasteride., when taking two capsules a week, you won't get anywhere near 95% Type II inhibition?

You'll probably get a little more inhibition of Type II than finasteride. everyday but you'll get more inhibition of Type I than you'd get from finasteride. everyday?

I have great respect for Bryans knowledge and experience on this subject, but the problem is that Bryans chart is not complete in it's labelling. Each line represents a constant % of steady state and the last few posts have concentrated on the 95% line. Reading your post you may have interpreted it as 95% of steady state Type II inhibition. Some one else may interpret it as 95% of the maximum drug achievable in the body if you continued to to take the drug for as long as it takes to reach maximum (like me). Others may have interpreted it as 95% of something else.

I 'thought' it was 95% of maximum achievable drug in the body at that dosage, but i could be wrong! This is the measurement my table is describing (as labelled above my table). I prefer to consider the trend line and describe the % of the peak of the plateau because i have trouble considering the drug level in the body to be 'steady-state' especially at low intakes of dutasteride (say 1 x 0.5 mg every 3 days).

To me steady-state is a dynamic condition where the input and output of a system are equal and therefore have no or little fluctuation. If there is a little fluctuation then the rate of the loss and gain must be equal. E.g, turn a water tap on and the amount entering = the amount leaving. Slight fluctuation (pulsating) example; a constant choked throttle on a spark ignition petrol engine where the air mass inducted by a cylinder = the air passing the throttle and entering the inlet manifold prior to the next induction stroke. This will cause a slight oscillation in the Manifold pressure which is relatively small compared with the absolute pressure itself, and can therefore be considered 'steady-state'.

However if we take the above example dutasteride (1 x 0.5 mg every 3 days) and assume a half life of 3 days (as suggested on other posts by Bryan AND this is consistent with his chart), my calculations indicate 95% of 'steady state' would occur at around 30 days which is also consistent with Bryans chart. This so called 'steady-state' condition involves the quantity of drug in the body dropping over 3 days to 0.525mg and jumping to 1.025mg in minutes when a cap is taken on the 3rd day. This oscillating cycle continues every 3 days where the rate of gain is substantially higher than the rate of loss. One value is double the other, the increase is almost instant and the decline is over 3 days and people call this 'steady state'. I would complain if the cruise control on my car or my central heating system did this and no one could convince me it was 'steady-state'!

 

[Timi]

In ouer Board some Men take One Cap all 7Days
with good results

with all Days Hair get bad (straw)

dutasteride is very strong i think a little Dose is the best
Grafics are sh*t

Timi

 

[Bryan]

That's a big mistake. As I explained in a previous post, the half-life at only two capsules/week isn't going to be anywhere near 35 days. That will throw-off your other calculations of the time it takes to approach steady-state.

My calculations are based on the only published data i have. Please point me towards the illusive data that describes the relationship between half life and quantity of drug in the body, size & frequency of intake etc i will adjust my models.

I can't give you any kind of formula that calculates the half-life from a given level of blood dutasteride, because such a thing wasn't provided in those dutasteride studies. Neither was there any kind of graph showing that. All they provided are just two data points: one where dutasteride has "a half-life of up to 5 weeks at high concentrations", to use their own words, and one where "as concentrations declined towards K(m) (0.96 ng/mL)....the half-life reduced to about 3 days". BTW, the blood level of 0.96 ng/mL corresponds to a daily intake of roughly 0.1 mg.

Having said all that, I took another look at their own chart showing time to achieve steady-state versus dose, and the figures you posted may not be so far off the mark, after all. Maybe it _does_ take more time than I thought to go from 95% to close to 100%. I probably didn't fully appreciate the "asymptotic" nature of going that last 5% of the way!

The data on your chart is insufficient because it assumes taking capsule sizes that dont exist.

Huh? Their graph shows the results for levels of intake that vary continuously all the way from 0.01 mg/day to 10 mg/day.

 

[Bryan]

Whoa dutasteride! Maybe I've always read Bryan's chart incorrectly but with the shorter half-life of dutasteride., when taking two capsules a week, you won't get anywhere near 95% Type II inhibition?

Well, clearly two capsules a week (0.143 mg/day) is somewhere between a 90% suppression (0.1 mg/day) and a 98%-99% suppression (0.5 mg/day). I'm guessing maybe 92%.

 

[Bryan]

This oscillating cycle continues every 3 days where the rate of gain is substantially higher than the rate of loss. One value is double the other, the increase is almost instant and the decline is over 3 days and people call this 'steady state'. I would complain if the cruise control on my car or my central heating system did this and no one could convince me it was 'steady-state'!

Even if your numbers are accurate, it's the mean values that we're talking about when we use the term "steady-state", not the short-term fluctuations.

 

[Timi]

Take finasteride Dayli for the Steady State
and all 5Days one dutasteride???

is that a Way?

Timi

 

[dut]

Even if your numbers are accurate, it's the mean values that we're talking about when we use the term "steady-state", not the short-term fluctuations.

In a previous post I described what I understood to be the meaning of steady state. I don’t believe that any highly transient system can be considered to be steady state. However, almost any transient system can have some form of mathematical filtering applied to achieve a smooth mathematical output despite the system itself being transient or even out of control.

I have given my reasons for describing the plateau of the trend line as a more technically correct way to describe what you call ‘steady state’.I know you prefer to take your information from official sources such as ‘journals’. However you may have a little more confidence if you know a little more about me. I have a PhD in mathematical modelling of Thermodynamic systems. My role is a Technical Specialist on Control Systems where I develop Matlab scripts that ensure certain objects travel from A to B without falling out of the sky! By no means am I trying to show off, expect respect or any thanks. I just want to give you confidence that I don’t talk crap except when it comes to Dutasteride!

I have looked up a few technical definitions of ‘steady state’ just in case I was wrong! There’s something really interesting at the end of this, and link provided as evidence.

steady state - (Also called steady motion, stationary motion.) A fluid motion in which the velocities at every point of the field are independent of time; streamlines and trajectories are identical. Sometimes it is further assumed that all other properties of the fluid (pressure, density, etc.) are also independent of time. All local derivatives in the fundamental equations then vanish.

Steady state: an open system that has no macroscopic changes; however, this is because any materials that leave the system are immediately replaced.

Steady state: A stable condition that does not change over time or in which change in one direction is continually balanced by change in another.

Steady state: A nonequilibrium state of a system through which matter is flowing and in which all components remain at a constant concentration.

Steady state: Frequently misused relating to drug levels within the blood reaching a plateau after repeated dosing at fixed intervals. Interesting one!

This is the VERY interesting one…… excusing Bryan’s use of the words…. but look at the last part in (brackets)!
Steady state: A state in which equilibrium has been achieved. In reference to antiepileptic drugs, steady state is achieved when a constant daily dose of a drug produces consistent blood levels of the drug (takes at least five times the half-life of the drug in question).

The above can be found at http://professionals.epilepsy.com/page/glossary.html#s which is not just from anyone one on a forum!

Note: 5 x 35 = something very close to 179

Bryan… I expect you will have gone from being sure that my plateau (or ‘steady state’) prediction is rediculously long, to plotting my data and realising it’s feasible, and now you’re dead certain! For your information the plateau being at least 5 x half life is obvious to any mathematician, and not open to opinion. By defintion it is mathematically impossible for a plateau to be reached within 5 x half life using a regular dose. The same is true for everything that has a half life.
Instead of thinking me as the competition, it may be worth considering how my mathematical expertise can complement your resource of knowledge.
Keep up the good work.
Assuring you of my best intentions at all times.

 

[dut]

The data on your chart is insufficient because it assumes taking capsule sizes that dont exist.

Huh? Their graph shows the results for levels of intake that vary continuously all the way from 0.01 mg/day to 10 mg/day.

Perhaps i didn't explain properly. I have only seen dutasteride in 0.5mg caps. The chart shows the effect of different dosages including less than 0.5mg.
I have taken the scale literally (ie; 0.05mg/day means what it says). You may have INTERPRETED this as achieved by taking 0.5mg every 10 days. These two alternatives may have differing results.

It would be good if you posted all links to original data so i can work out half lives for all regular dosage regimes etc. I have been to the site where you store some data but do not know how to list a directory of info. You may laugh but I have had to guess by adjusting the numbers at the end of your links :$

 

[Old Baldy]

Whoa dutasteride! Maybe I've always read Bryan's chart incorrectly but with the shorter half-life of dutasteride., when taking two capsules a week, you won't get anywhere near 95% Type II inhibition?

Well, clearly two capsules a week (0.143 mg/day) is somewhere between a 90% suppression (0.1 mg/day) and a 98%-99% suppression (0.5 mg/day). I'm guessing maybe 92%.

Bryan and dutasteride, the chart at hairsite indicates 80 percent serum reduction when 0.5mg of dutasteride. is taken every other day. I have to go back to your chart and look more closely.

Da** Bryan and dutasteride. I guess I've always read Bryan's chart incorrectly. If I make a straight line from the 1.4mg/day point I only get to around 80 percent inhibition. I must be reading that chart wrong all this time? I just don't see a steady state of 90-95 percent with 1.4mg/day. :blush:

I thought like you dutasteride. when you said you could max out at 95 percent inhibition and would never get nearly that high of a steady state inhibition rate with 1.4mg/day when looking at Bryan's chart?? I MUST be reading his chart incorrectly all this time.

 

[Bryan]

Even if your numbers are accurate, it's the mean values that we're talking about when we use the term "steady-state", not the short-term fluctuations.

In a previous post I described what I understood to be the meaning of steady state. I don’t believe that any highly transient system can be considered to be steady state.

But exactly HOW MUCH transience are you personally willing to accept, before you conclude that a system has lost its condition of being "steady-state"?

Even when taking dutasteride at the standard, approved dosage (1 Avodart capsule per day), there is STILL a very small amount of daily fluctuation in DHT levels, although it's obviously much smaller than when you take (say) only 1 capsule every third or fourth or fifth day.

I see no reason not to continue to use the term "steady-state", even in the context of relatively wide daily fluctuations when a relatively larger dose is used intermittently (every few days). We all know exactly what we mean when we use that term, even though we're using it more loosely here in this context.

Bryan… I expect you will have gone from being sure that my plateau (or ‘steady state’) prediction is rediculously long, to plotting my data and realising it’s feasible, and now you’re dead certain! For your information the plateau being at least 5 x half life is obvious to any mathematician, and not open to opinion. By defintion it is mathematically impossible for a plateau to be reached within 5 x half life using a regular dose. The same is true for everything that has a half life.

Actually, I realized I had made a mistake when I took a closer look at the published graph, and saw how the amount of time it took to go from 70% of steady-state to 90% to 95% was so nonlinear. I then realized the "asymptotic" nature of the progression, and that you were probably correct in your calculations.

 

[Bryan]

The data on your chart is insufficient because it assumes taking capsule sizes that dont exist.

Huh? Their graph shows the results for levels of intake that vary continuously all the way from 0.01 mg/day to 10 mg/day.

Perhaps i didn't explain properly. I have only seen dutasteride in 0.5mg caps. The chart shows the effect of different dosages including less than 0.5mg.
I have taken the scale literally (ie; 0.05mg/day means what it says). You may have INTERPRETED this as achieved by taking 0.5mg every 10 days. These two alternatives may have differing results.

Surely you don't expect them to produce a graph showing time to achieve steady-state, even for every possible intermittent usage of Avodart capsules, do you?

For our modest purposes, we don't have much choice except to convert the intermittent use of Avodart into an equivalent daily dose, and use THAT value when consulting those graphs and charts. I don't think that strategy is too far off the mark.

It would be good if you posted all links to original data so i can work out half lives for all regular dosage regimes etc. I have been to the site where you store some data but do not know how to list a directory of info. You may laugh but I have had to guess by adjusting the numbers at the end of your links :$

I'm not quite sure what you mean, or what you're requesting. Are you saying you'd like a complete list of all the links to the graphs I've posted from the Gisleskog et al studies on dutasteride and finasteride?

 

[Bryan]

Da** Bryan and dutasteride. I guess I've always read Bryan's chart incorrectly. If I make a straight line from the 1.4mg/day point I only get to around 80 percent inhibition. I must be reading that chart wrong all this time? I just don't see a steady state of 90-95 percent with 1.4mg/day. :blush:

I thought like you dutasteride. when you said you could max out at 95 percent inhibition and would never get nearly that high of a steady state inhibition rate with 1.4mg/day when looking at Bryan's chart?? I MUST be reading his chart incorrectly all this time.

I'm completely lost! Which chart are you talking about??

 

[Old Baldy]

Bryan: Is this "your" chart that, IIRC, you've posted before? (It's been a LONG time since I've seen it, so maybe I've forgotten your explanation on how to interpret it?)

http://www.geocities.com/bryan50001/dutasteride3.htm

The other chart, (i.e., the chart that shows 80 percent inhibition), is from another "hairsite" and was an extrapolation made by another member IIRC? That 80 percent inhibition rate is from a dosage of 0.5mg every other day.

At first, I was relying on the "hairsite" chart then read your post and went to what I think is your "geocities" chart and realized that was a chart you've posted many times over the years IIRC?

I think I've forgotten how to interpret your "geocities" chart. :blush:

Sorry for the confusion. I was "mixing" the charts in my previous post and didn't make it clear that I'm having a hard time extrapolating estimated time to achieve steady state at 1.4mg/day dosage AND how much inhibition we would reach at steady state, (i.e., when I look at your geocities chart).

I mean, your geocities chart doesn't seem to show 1.4mg/day ever reaching a "horizontal" line which, I assume means "steady state"? So, I'm having a hard time predicting when that would happen with 1.4mg/day when looking at the geocities chart and how much inhibition there would be at 1.4mg/day.

I hope I'm making my confusion a little clearer? Totally disregard my previous post, it was "off the wall". I was mixing the charts in my confused mind and was out in leftfield.

I can see now, after re-reading my previous post that it was gibberish. Sorry! :blush:

 

[Bryan]

Bryan: Is this "your" chart that, IIRC, you've posted before? (It's been a LONG time since I've seen it, so maybe I've forgotten your explanation on how to interpret it?)

http://www.geocities.com/bryan50001/dutasteride3.htm

Oh yeah, that's "my" chart, alright (from the Gisleskog et al studies), but all it deals with is time to achieve steady-state versus dose. It has nothing whatsoever to do with 5a-reductase inhibition!

The other chart, (i.e., the chart that shows 80 percent inhibition), is from another "hairsite" and was an extrapolation made by another member IIRC? That 80 percent inhibition rate is from a dosage of 0.5mg every other day.

At first, I was relying on the "hairsite" chart then read your post and went to what I think is your "geocities" chart and realized that was a chart you've posted many times over the years IIRC?

I think I've forgotten how to interpret your "geocities" chart. :blush:

Sorry for the confusion. I was "mixing" the charts in my previous post and didn't make it clear that I'm having a hard time extrapolating estimated time to achieve steady state at 1.4mg/day dosage AND how much inhibition we would reach at steady state, (i.e., when I look at your geocities chart).

I mean, your geocities chart doesn't seem to show 1.4mg/day ever reaching a "horizontal" line which, I assume means "steady state"? So, I'm having a hard time predicting when that would happen with 1.4mg/day when looking at the geocities chart and how much inhibition there would be at 1.4mg/day.

Hitting a horizontal line on this particular graph doesn't have anything to do with anything (although a horizontal line at the 1.4 mg/day dose DOES hit horizontal lines for all three of the percentages on the graph (70%, 90%, and 95%). But you can see from the graph that that particular dosage hits those percentages (respectively) at about 40 days, 83 days, and 110 days, which is all that matters.

To find out how much inhibition you get of the type 2 enzyme at a dose of 1.4 mg/day (why are you so interested in that specific dose, anyway? ), you'd have to look at the other graphs which show inhibition. There's even a line for the specific dose of 1 mg/day on those other graphs, which is darned close to what you're looking for. The inhibition for your 1.4 mg/day dose should be right around 99% or so, I would imagine.

 

[Andrea]

A the end:
2 caps/week is a right dosage after your system is in "steady state"?

 

[Bryan]

A the end:
2 caps/week is a right dosage after your system is in "steady state"?

You understand that each different dosage will have its own steady-state, right?

 

[dut]

But exactly HOW MUCH transience are you personally willing to accept, before you conclude that a system has lost its condition of being "steady-state"?

That's a good question and i dont know an 'official' answer.
Lets look at the definitions and high light (bold) where we would fail to be able to use the term in the example of dutasteride (especially at low doses).

Steady state: an open system that has no macroscopic changes; however, this is because any materials that leave the system are immediately replaced.
Steady state: A stable condition that does not change over time or in which change in one direction is continually balanced by change in another.
Steady state: A nonequilibrium state of a system through which matter is flowing and in which all components remain at a constant concentration.

I would say that if the deviation was only a few percent and the rate of loss and gain were within few percent of each other then you could argue the condition was 'steady state'.
There are many mathematical methods such as std deviation, Coeficient Of Variation (COV), 'R' values in curve fitting etc. However, i don't think anyone could stretch the interpretation of the above definitions to consider that dutasteride levels in the body when taking 2/week was 'steady state'.

 

[Bryan]

But exactly HOW MUCH transience are you personally willing to accept, before you conclude that a system has lost its condition of being "steady-state"?

That's a good question and i dont know an 'official' answer.

I would say that if the deviation was only a few percent and the rate of loss and gain were within few percent of each other then you could argue the condition was 'steady state'.

Take a look at the following graphs:

http://www.geocities.com/bryan50001/dutasteride2b.htm

Scroll down to Figure 7 near the bottom, and look at the graph on the lower left where dutasteride is given in the form of 2.5 mg, once a week. Now look at the TOP curve in that group of curves, the one with the must fluctuation. Would you consider that particular one as being at steady-state?

However, i don't think anyone could stretch the interpretation of the above definitions to consider that dutasteride levels in the body when taking 2/week was 'steady state'.

I would. I don't have any objection to using the term more loosely like that, since we all understand what we mean when we say that.

 

[Old Baldy]

Bryan wrote:

Hitting a horizontal line on this particular graph doesn't have anything to do with anything (although a horizontal line at the 1.4 mg/day dose DOES hit horizontal lines for all three of the percentages on the graph (70%, 90%, and 95%). But you can see from the graph that that particular dosage hits those percentages (respectively) at about 40 days, 83 days, and 110 days, which is all that matters.

To find out how much inhibition you get of the type 2 enzyme at a dose of 1.4 mg/day (why are you so interested in that specific dose, anyway? ), you'd have to look at the other graphs which show inhibition. There's even a line for the specific dose of 1 mg/day on those other graphs, which is darned close to what you're looking for. The inhibition for your 1.4 mg/day dose should be right around 99% or so, I would imagine.

Those are different charts than the one I always see people linking to (i.e., the multiple chart link you provided dutasteride. above are new to me). The one that confused me is the one in my post. That's the chart I've seen linked to so many times in the past.

Never saw your charts referred to in the link you gave dutasteride. in the post above. Thanks for the post. I see what you mean. (Glad I was confused when I thought you were getting inhibition rates from the chart I linked! I kept saying to myself, "how in the heck does Bryan get inhibition rates from this chart?! )

Sorry Bryan, I meant 0.14 mg/day. :blush: (I've gotta be CONCISE if I expect people to have any idea what the heck I'm talking about for Godsakes. :blush: )

I'm taking two duts. a week now instead of using dutasteride. in topical solutions. (I figured I was getting about that much into my system from topical use anyways?)

Those mulitiple charts help alot!

I still use my 5 percent homemade spironolactone. concoction very regularly though.

Things are doing ok with this combination of androgen "medications".

Thanks for the other charts and explanation. (If I ever saw your link to multiple charts, I've forgotten.)

Thanks again.

(And yes Bryan, I would consider the 2.5mg/once a week in Figure 7 to be steady state for those individuals. Even the top one. It ain't that much of a deviation IMHO. It's interesting that, at 10mg/once a month, some people achieved steady state.)

 

[dut]

Take a look at the following graphs:

http://www.geocities.com/bryan50001/dutasteride2b.htm

Scroll down to Figure 7 near the bottom, and look at the graph on the lower left where dutasteride is given in the form of 2.5 mg, once a week. Now look at the TOP curve in that group of curves, the one with the must fluctuation. Would you consider that particular one as being at steady-state?

I would say that all of them except the bottom right a relatively steady - a small (not macroscopic) fluctuation around an already large deflection. However, i have never queried whether DHT levels are relatively steady, i have always qualified my concerns with using the term when discussing the level of change of the DRUG ITSELF in the body, as per my interpretation of the chart with your pencilled in line which does not mention DHT.

I would. I don't have any objection to using the term more loosely like that, since we all understand what we mean when we say that.

I would agree that you are using the term loosely and we all know what you mean by it (when the moving average trend line has plateued).

So can you confirm. Is the chart (with the 0.5mg pencil line) describing 'steady state' drug level in the body?

Also more and more links with data are coming out of the woodwork. Can you please post a full list of study/prediction links of original data where possible. You may have done it before but i've not been here long.

Now, I have a question for you. Is there a financially viable test (may be blood test) that may suggest/infer if DHT levels are low enough to not play a significant role in male pattern baldness after taking a drug?