Dutasteride Study.

[eliazush]

Hi Bryan,

Ok, I will look for the complete assay you referred me to. Thanks.

However, some points are still unclear to me. I looked at the graphs. They describe the DHT levels in the serum depending on the dose/medication. Now think about the levels of dutasteride in the blood.
dutasteride has a very long half life, meaning it takes a few weeks till its concnetration in the body goes down to half. So, with such long hald life, its levels accumulates in time. For example: let's take a patient who takes 0.5mg daily. On the second day almost all drug is still in his body. Then he takes another pill. So now he's got almost twice as much. And so on. The body keeps eliminating the drug but more and more is consumed, and because the rate of consuming is higher than the rate of elimination accumulation is occuring.

What's weird to me is that even though more DHT is produced because of the ihibition made by dutasteride (like you suggested), more drug has accumlulated by that time (till it acheives its stady state, which happens after about 4 half lives, in this case after 6 weeks times 4 - about half a year) So...I expect to see DHT levels going down over time due to cummulating levels of dutasteride till the steady state. And this phenomenos is not shown in the graphs.

I don't doubt these graphs because I understand they are based on real experiment. I am just wondering and looking for explainations. Do you have any suggestions??

 

[eliazush]

Also, I am now seeing they say "predicted" levels under each graph. What is "predicted"?? They didn't measure real blood levels here??

 

[sam-]

http://www.regrowth.com/hairloss-remedy ... esults.cfm

Testosterone increased 4.4% for Finasteride, 6.4% for 0.05mg Dutasteride, 16% for 0.1mg Dutasteride, and 27% for 0.5mg and 2.5mg Dutasteride. Although the rise in Testosterone may seem high, the Testosterone levels were almost always within normal range according to Rittmaster.

I thought those medicines reduce Testosterone level not increase it :!:
Then why the sex drive decreases when using them :!:

Read this about Testosterone:
http://www.abc.net.au/science/slab/testost/story.htm

 

[Bryan]

However, some points are still unclear to me. I looked at the graphs. They describe the DHT levels in the serum depending on the dose/medication. Now think about the levels of dutasteride in the blood.
dutasteride has a very long half life, meaning it takes a few weeks till its concnetration in the body goes down to half. So, with such long hald life, its levels accumulates in time. For example: let's take a patient who takes 0.5mg daily. On the second day almost all drug is still in his body. Then he takes another pill. So now he's got almost twice as much. And so on. The body keeps eliminating the drug but more and more is consumed, and because the rate of consuming is higher than the rate of elimination accumulation is occuring.

No, that's not correct. The level of dutasteride in the blood builds up gradually at first, but it eventually reaches a point where the elimination equals the consumption, and a "steady-state" is achieved. Here's an excerpt from near the end of the first study:

"Even though a major nonlinearity exists in the elimination of GI198745, the presence of a linear elimination pathway ensures that unlimited accumulation will not take place."

What's weird to me is that even though more DHT is produced because of the ihibition made by dutasteride (like you suggested), more drug has accumlulated by that time (till it acheives its stady state, which happens after about 4 half lives, in this case after 6 weeks times 4 - about half a year) So...I expect to see DHT levels going down over time due to cummulating levels of dutasteride till the steady state. And this phenomenos is not shown in the graphs.

Yes, it IS shown in the graphs. You can plainly see that DHT suppression levels over a period of 28 days (see Fig. 6) asymptotically approach a fixed limit, which varies from dose to dose.

Bryan

 

[Bryan]

Also, I am now seeing they say "predicted" levels under each graph. What is "predicted"?? They didn't measure real blood levels here??

They didn't actually perform real-life trials by giving subjects daily, weekly, and monthly doses of dutasteride and then measuring their serum DHT levels along the way. Those are graphs of COMPUTER SIMULATIONS of what such trials would produce, based on their lengthy and careful measurements of dutasteride doses that they DID give to real-life test subjects.

BTW, they said that their resulting modeling and differential equations of the pharmacokinteics of dutasteride allowed them to make further predictions (like those computer simulations) that have an error of no more than 3%.

Bryan

 

[Cornholio]

I thought those medicines reduce Testosterone level not increase it :!:
Then why the sex drive decreases when using them :!:

DHT and Testosterone are both androgens, though DHT is 10 x as potent as testosterone. Finasteride and Dutasteride block the conversion of testosterone to DHT. The pituitary gland senses this decrease in androgens and responds by stimulating the production of more testosterone so that testosterone goes up but overall androgen activity (which is the sum of DHT and testosterone activity) goes down. That is why there is reduced sex drive and some gynecomastia...

 

[everysixseconds]

I thought those medicines reduce Testosterone level not increase it :!:
Then why the sex drive decreases when using them :!:

DHT and Testosterone are both androgens, though DHT is 10 x as potent as testosterone. Finasteride and Dutasteride block the conversion of testosterone to DHT. The pituitary gland senses this decrease in androgens and responds by stimulating the production of more testosterone so that testosterone goes up but overall androgen activity (which is the sum of DHT and testosterone activity) goes down. That is why there is reduced sex drive and some gynecomastia...

i thought it was just the testosterone that should have normally been converted to DHT (but isnt due to 5AR inhibition) that raises testosterone levels?????

 

[Bryan]

That's a simplistic way of looking at it that everybody always ASSUMES is the explanation. But the fact is that LH (luteinizing hormone) levels increase by about the same amount as testosterone, indicating that the brain is actually REQUESTING additional testosterone...it's not just because less T is being converted to DHT.

Bryan