Discussion in 'Antiandrogens - Propecia, Dutasteride, etc.' started by philly, Oct 28, 2007.
1.5 hrs? Where did you see that? The monograph says that "mean terminal half-life is approximately 5-6 hours in men 18-60 years of age and 8 hours in men more than 70 years of age."
Lets ignore where you got your figures from and just discuss the concept....
What you describe is a well know practice with dutasteride. It would appear that 0.5mg of dutasteride/week (0.071mg/day) is thought to be as effective as 5mg/day finasteride.
The half life of dutasteride is so long that it is generally accepted that once the level of dutasteride has built up and stabilised you can take your 1 capsule/week and there will be an insignificant fluctuation (saw tooth) around a high stabilsed nominal level of dutasteride in the body.
This same principle must happen with finasteride but the half life is so short that the 24hr fluctuation is highly significant. In order to achieve a stabilsed 'smooth' level of finasteride in a similar way to dutasteride you would have to drip feed it! In practical terms you might consider splitting your 1mg pill in to 4 pieces (4 quarters per day) which is not easy if you were already splitting a 5mg tab!
The question is... What is best? (1) a fluctuation of finasteride in the body from very low (circa 0.1mg) to very high (1mg) each day OR (2) drip feed the 1mg over 24hrs to achieve a stable 0.3mg in the body?
I dont know the answer. Anyone else know?
You can get a reasonable "guesstimate" of that by taking a look at my famous finasteride/serum DHT graph which has been posted and re-posted over the years! Check it out:
Although those are just serum levels of DHT after various SINGLE doses of finasteride, nevertheless I think you can get some reasonable idea of what the day-to-day fluctuation of DHT is when taking daily doses of finasteride, just by looking at the upward slope of those lines.
Your estimate of "10%" for the variation seems reasonable to me, but it's anybody's guess how much extra benefit you'd get by reducing that to (say) 5%.
Don't forget the OTHER factor which plays an even larger role in determining the daily fluctuation in serum DHT levels: the regeneration of the 5a-reductase type 2 enzyme after it's been destroyed by finasteride is itself quite slow. That's a very significant factor is keeping the DHT level from rising back up again very fast, REGARDLESS of whether or not there's any finasteride still around.
Taking only 1 Avodart capsule per week isn't going to result in a very high level of the drug in the blood, and the half-life will drop-off considerably at that low a level. I think it's pushing it quite a bit to take it that infrequently. I'd probably recommend an Avodart capsule twice a week as being the minimum dose, for that reason.
I've done a few cals in exel. All are based on the amount of finasteride in the body NOT DHT levels.
Assuming a finasteride Half life of 6hrs, any regime reaches 90% of maximum within 1 day.
Taking 1mg per day has a fluctuation of 0.07 to 1.07 mg in the body.
Taking 0.25mg every 6 hrs has a fluctation of 0.25 to 0.5mg.
Dont want to insult the mathematicians but anyone who wants to plot this in exel can follow this..
a) Start with the 1st dose and mulitiply it by 0.5 every 6hrs to get the residual amount in the body.
b) Add the 2nd dose to the residual and multiply by 0.5 the total every 6hrs to get the new residual.
c) Repeat (b) for every dose taken. Don't bother doing more than 2 days worth of calculations - your at the maximum!
The same calcs can be done for dutasteride but you need to multiply by 0.98 every day to get something equivalent to a half life of 35 days.
Bryan. I don't understand your comment --
I'm not saying you're wrong but i'd like to understnd. Why does half life change considerably with dosage?
Any interpolated data i have seen shows 0.5mg dutasteride per week to well exceed the performance of the standards 1mg finasteride per day dosage. Also 0.1mg dutasteride per day exceeds the performance of a full 5mg of finasteride!
I do actually take 2 x 0.5mg per week but started by taking 15 tabs (1 per day for 15 days) to get me to the stabilsed condition in 15 days instead of building up over 3 months! I've gained loadsa hair in 6 months. My plan is to drop down to one tab per week after 1 year.
I agree and i'm guessing that all 4 posting on this thread have the intellect to understand this. As a mathematical modeller on control systems i usually use matlab but thought i'd explain how to do it in exel to allow most people to plot their own data. The calculator method is a little long winded with dutasteride unless you take it every 35 days!
It doesn't matter how well we understand the maths, the problem is that we dont understand how the mg osscilation of the drug in the body (compound effect of frequency, amplitude etc) affects DHT and ultimately hair because the relationship it is little more remote!
Sorry if i'm starting to write rubbish. The Rioja was great and compliments the nizoral/Ket, Mon and dutasteride well on a sunday evening. I've convinced the wife that it's all part of the plan!
Heh. Yeah, I almost posted those same graphs, too, because they clearly show that daily "sawtooth" variation in inhibition with finasteride, and it's close to the same figure you originally quoted of 10%. But finally I decided that the older graph I posted was good enough for my modest purposes.
Again, I don't know if I'd call it "a lot" or "rapid". Rapid, compared to WHAT, exactly? Glacier movement? After all, as I've been saying for years on hairloss sites, it does take a week or two for DHT levels to get back to normal after the last dose of finasteride.
What "experiment" are you talking about??
I've never ever made the claim that 5AR1 has no effect at all on hairloss, just that it's not nearly as important as 5AR2. Anything that reduces even serum DHT (like a specific 5AR1 inhibitor) will have _some_ beneficial effect on hair, because a few of those serum DHT molecules will inevitably get into hair follicles.
I don't think that's the ONLY reason. Otherwise, it would be hard to explain why 2.5 mg/day of dutasteride does noticeably better than only 0.5 mg/day. It's hard to imagine that a virtually TOTAL suppression of 5AR2 (like you'd have with the larger dose) would be that much better than the 98%-99% suppression that you get with the standard dose. I think that the rest of the difference in hair results is indeed due to the (partial) inhibition of the type 1 enzyme.
If it had a shorter half-life, it wouldn't be as effective as it is at inhibiting EITHER of the 5a-reductase enzymes!
Go back to him and ask him to justify that claim!! Has he been reading Armando's posts?
I've never heard such a claim. If you can find that article again, I'd REALLY like to read it!! :woot:
Dutastride has very non-linear elimination characteristics due to the fact that there are two separate pathways of elimination, and the first of them (the saturable pathway) gets saturated pretty early in the game, as you're gradually increasing the dose. Just to give you some idea of how the half-life changes with dose, at an intake level of 0.1 mg/day, the half-life of dutasteride drops to roughly about three days or so.