Why Doesn't GSK Just Develop a Type II.....

[doggfather]

Why doesn't GSK just develop a type II 5-alpha reductase inhibitor that has the power/effect of dutasteride's type II inhibiting capability but without inhibiting type I 5-alpha reductase so to avoid the possibility of long-term neurological side effects? Is there anything in the pipeline like this where they can almost inhibit all type-2 formed DHT without touching type-1 formed DHT? Sort of like a super finasteride sans the increased side effects of consuming gobs of finasteride.

 

[Bryan]

Why do you assume that there would be increased side-effects from consuming gobs of finasteride, and even if that DID happen, why do you assume that you wouldn't get the SAME side-effects from using a "super-finasteride"??

 

[doggfather]

If I recall correctly, didn't Proscar (5mg) have a higher % of side effects than 1mg? So I just assumed that taking more finasteride than the standard 1mg might cause a higher chance of getting side effects. And about the super finasteride, that was in reference to 0.5mg dutasteride which in some study seemed to have less percentage of side effects than 5mg of finasteride even though the dutasteride reduced dht levels more.

But what i really want to know is why glaxo or whomever can't develop a drug that inhibits the type II 5 alpha reductase as effectively as dutasteride without inhibiting the type I 5-alpha reductase so people wouldn't have to be concerned about taking a drug that would affect their brain.

 

[Bryan]

If I recall correctly, didn't Proscar (5mg) have a higher % of side effects than 1mg? So I just assumed that taking more finasteride than the standard 1mg might cause a higher chance of getting side effects. And about the super finasteride, that was in reference to 0.5mg dutasteride which in some study seemed to have less percentage of side effects than 5mg of finasteride even though the dutasteride reduced dht levels more.

In regard to side-effects, I'm not sure about Proscar versus Propecia. I believe they're about the same, which would fit right in with my general feeling that side-effects should be proportional to 5a-reduction, not the quantity of the drug per se (at these low levels of drug intake, anyway).

But what i really want to know is why glaxo or whomever can't develop a drug that inhibits the type II 5 alpha reductase as effectively as dutasteride without inhibiting the type I 5-alpha reductase so people wouldn't have to be concerned about taking a drug that would affect their brain.

Yeah, I've wondered about that, myself. I think those companies probably feel that the ~90% inhibition that you get with Proscar is sufficient, so there's no particular need to develop yet another drug. Of course, you can always kick the inhibition up another notch or two (or however many notches you want) by increasing the finasteride dose, but you _will_ start to gradually inhibit the type 1 enzyme at really large doses. Gisleskog et al in those dutasteride studies I've posted about say the following in the Discussion section at the end:

...finasteride has been shown to interact with 5a-reductase type 1 in vitro with a second-order rate about 2.2% of the rate constant for the GI198745--5a-reductase type 1 interaction....a steady-state finasteride concentration of 1200 ng/mL would be needed to suppress 5a-reductase type 1 by 50%. Assuming linear pharmacokinetics, daily doses of about 270 mg finasteride would be required to achieve average concentrations of this magnitude.

My own guesstimate is that a Proscar tablet four times a day, for a total of 20 mg/day (spread throughout the day, not taken all at once) ought to come reasonably close to dutasteride inhibition of the type 2 enzyme, without affecting the type 1 enzyme too awfully much.

Bryan

 

[blaze]

If you take 0.5mg of dutasteride everyday that inhibits about 98% type 2 5 alpha reductase, doesnt it?

The phase 2 FDA trials for dutasteride were conducted with dosages of 2.5mg per day. That is 5 times as much as the standard 0.5mg capsule per day that people on hairloss boards take. How much of the type 2 enzyme does that inhibit and how much of the type 1 enzyme does that inhibit?

Maybe thats why they stopped the FDA trials for dutasteride at 2.5 mg per day because it inhibited too much of the type 1 enzyme. If 0.5mg of dutasteride per day inhibits about 50% of the type 1 enzyme, how much more would 2.5mg per day inhibit? 75%? If so, thats alot.