A question about half life of Avodart

[ecs]

From what I read on a web page(Authorr. Edwin S. Epstein) the half life of Avodart in mens' body is about 240 hrs (10days), does it mean we can take it once per say 5-6 days or more?

 

[stax]

To add, if iv been on Avodart for 21 days at 0.5mg per day, will it be totally out of my system in 10 days?


ecs, from what ive read, if you take one 0.5mg Avodart pill every 5 days, your DHT levels will be the same as if you took 5mg Proscar daily.

 

[Bryan]

The half-life of dutasteride varies considerably, depending on the concentration in your bloodstream. When it's reached "steady-state" at the recommended dose of one Avodart/day (like when you've been taking it that way for several weeks or months), the half-life can be up to about 5 weeks long. On the other hand, when it's reached steady-state at a dose of only 0.1 mg/day, the half-life is only around two or three days. That's because dutasteride has nonlinear elimination characteristics. It's eliminated considerably faster (relatively speaking) at lower blood concentrations.

Bryan

 

[CCS]

thanks for the information

I did the math and the costant 5 week half life did not add up. I knew it had to be non-linear, but I did not know it varied that much. I don't know why they can call it a half life then.

In response to the first guys question, yes you can take it every 5 days, but your blood concentration will be very low, and also you DHT inhibition. I have some graphs I saved off some web pages. I'll upload them on this site if someone tells me how to do so off my computer, since I don't have the web site.

The graph shows the blood concentration for 0.5mg/day, 0.5mg/ever other day, and 0.5mg two days on, one day off. Equilibrium concentration is proportional to dose in each, which shows that at these doses, half lives are about the same. It does not show it for lower doses like the other guy mentioned (0.01 was it?), so I don't know how to predict 0.1mg/day. I'm sure the steady state concentration for 0.1 is published someowhere. If you tell me what it is, I have another graph that relates DHT inhibition to serum concentration.

If I guess that 0.1mg/day leads to, say, 1/10th the steady state of 0.5mg/day, then that means 3.2ng/mL, which translates to about 50% DHT inhibition.

 

[Bryan]

Re: thanks for the information

I did the math and the costant 5 week half life did not add up. I knew it had to be non-linear, but I did not know it varied that much. I don't know why they can call it a half life then.

I agree with you that it's a little misleading. It's sort of an instantaneous, calculated half-life at a specific point in time, if you catch my drift! :wink:

In response to the first guys question, yes you can take it every 5 days, but your blood concentration will be very low, and also you DHT inhibition.

Uhh.....nobody here has bothered to specify what DOSE it is that's being discussed. Just because dutasteride has a long half-life, that doesn't mean you can cheat the system by taking only a single Avodart capsule once every 5 days, and still get the same results as when you take an Avodart capsule every day! What it means is that you can take 5 Avodart capsules every 5 days, and get the same results. You always have to take the same AVERAGE dose, but the long half-life allows for very flexible dosing schedules as regarding how OFTEN you take it. For example, you can take 0.5 mg every day, or you can take 1 mg every other day, or you can take 3.5 mg once a week, or you can take 7 mg every two weeks. See my point?

The graph shows the blood concentration for 0.5mg/day, 0.5mg/ever other day, and 0.5mg two days on, one day off. Equilibrium concentration is proportional to dose in each, which shows that at these doses, half lives are about the same. It does not show it for lower doses like the other guy mentioned (0.01 was it?), so I don't know how to predict 0.1mg/day.

Here's the info straight from Gisleskog:

Pharmacokinetics. In this study, the pharmacokinetics of GI198745 have been described with a 2-compartment model with 2 parallel elimination pathways--a linear and a nonlinear pathway. At high concentrations the linear pathway dominates as the route of elimination, giving a clearance of of 0.58 L/h, which combined with the large volume of distribution (511 L) gives a terminal half-life of up to 5 weeks. As concentrations declined toward the concentration at which the saturable elimination pathway operates at half maximal rate (Km) (0.96 ng/mL), the proportion eliminated through the relatively rapid saturable elimination pathway increased, and the half-life decreased to about 3 days. This marked decrease in half-life was a consequence of the relatively high clearance (6.2 L/h) of the saturable pathway at low concentrations.

The only thing that needs to be added here is that the concentration they mention above as having a half-life of only about 3 days (0.96 ng/mL) is approximately the concentration you get when taking 0.1 mg/day of dutasteride.

If I guess that 0.1mg/day leads to, say, 1/10th the steady state of 0.5mg/day, then that means 3.2ng/mL, which translates to about 50% DHT inhibition.

That's not too far off the mark.

Bryan