Topical vs Oral Avodart
- Thread starter Tombolino
- Start date
Here are my calculations
The problem with aloe vera is it is water based, and dutasteride is not water soluble. Even if you mix in the dutasteride, only the dutasteride in contact with skin will go in. The rest will not diffuse through the aloe to the skin because of insolubility. You'd have better odds with petroleum jelley, though the viscosity is so high that the diffusion from the surface of the jelly to the skin would take forever. This would help with time release. I doubt that high dose of aloe on your skin for so long is healthy.
1/3 of topical testosterone is absorbed from patches, and they are worn 23 hours per day, I think. Dusteride would probably have a lower absorption rate because it is bigger (extra benzene ring), if it were in a cream patch. It would do much better in minoxidil. It is perfectly stable in a minoxidil solution. The lower the concentration of a topical (increases fraction absorbed, not amount), and the slower the evaporation of the solution (more time to absorb), and the lower the viscosity of the solution (affects diffusion rate from top of liquid to bottom where contacts the skin), the higher the percentage of the dose will be absorbed. It also helps if the dutasteride is not significantly more soluble in the solution than in the skin, or it will want to stay in solution and only a little will go in the skin. The water and glycol in minoxidil slow the evaporation rate, giving time for absorption, though the glycol makes the skin more permeable and is responsible for all irritation.
I know with my chemical research that if you squirt 2-4 capsules into your minoxidil bottle, you will get enough in your skin to have the equivalent of 2.5+ mg orally. I don't know if it will stay in high concentration in the skin before slowly leaving, or if it will get rinsed away by blood so fast that your scalp only has the high dose for an hour or less, and your body just gets a lower dose (the fraction that entered the skin) than it would from oral. At least the dutasteride would take every R5 with it on its way out of the scalp, and dutasteride, unlike finasteride, does not let go of R5. We need to apply it topically and then have a Doctor test the dutasteride levels in our scalp 1, 4, and 11 hours after the minoxidil application. We also need to know serum levels because we don't know how much scalp DHT comes from body serum and how much is locally produced in the scalp. The scalp has about 1/200th the volume of the body, based on 400 cm3 of scalp vs 80kg of body. male pattern baldness area is 200cm3. So 1 capsule in minoxidil applied over 30 days would give the scalp the equivalent of 0.5*200/30 = 3.33 mg oral, while the body gets 0.5/30 = 0.017 mg of used dutasteride/scalpR5 complex for less side effects. Only 60% is absorbed in the intestine, and probably only 1/5 would penitrate the scalp. The question is how fast would the blood in the scalp rinse away the dutasteride. The worse a man's scalp circulation, the longer it stays there for him. I think 2-4 capsules in 1 minoxidil bottle would do fine. Apply 2 times a day, or use 2% 3 times for a more even dose. The concentration of dutasteride in the bottle is so much lower than that of the minoxidil that I'm sure it will almost all go in.
This is MUCH cheaper than 30 capsules a month, so buy the real Avodart at Walgreens in person and know you are getting real dutasteride.
The problem with aloe vera is it is water based, and dutasteride is not water soluble. Even if you mix in the dutasteride, only the dutasteride in contact with skin will go in. The rest will not diffuse through the aloe to the skin because of insolubility. You'd have better odds with petroleum jelley, though the viscosity is so high that the diffusion from the surface of the jelly to the skin would take forever. This would help with time release. I doubt that high dose of aloe on your skin for so long is healthy.
1/3 of topical testosterone is absorbed from patches, and they are worn 23 hours per day, I think. Dusteride would probably have a lower absorption rate because it is bigger (extra benzene ring), if it were in a cream patch. It would do much better in minoxidil. It is perfectly stable in a minoxidil solution. The lower the concentration of a topical (increases fraction absorbed, not amount), and the slower the evaporation of the solution (more time to absorb), and the lower the viscosity of the solution (affects diffusion rate from top of liquid to bottom where contacts the skin), the higher the percentage of the dose will be absorbed. It also helps if the dutasteride is not significantly more soluble in the solution than in the skin, or it will want to stay in solution and only a little will go in the skin. The water and glycol in minoxidil slow the evaporation rate, giving time for absorption, though the glycol makes the skin more permeable and is responsible for all irritation.
I know with my chemical research that if you squirt 2-4 capsules into your minoxidil bottle, you will get enough in your skin to have the equivalent of 2.5+ mg orally. I don't know if it will stay in high concentration in the skin before slowly leaving, or if it will get rinsed away by blood so fast that your scalp only has the high dose for an hour or less, and your body just gets a lower dose (the fraction that entered the skin) than it would from oral. At least the dutasteride would take every R5 with it on its way out of the scalp, and dutasteride, unlike finasteride, does not let go of R5. We need to apply it topically and then have a Doctor test the dutasteride levels in our scalp 1, 4, and 11 hours after the minoxidil application. We also need to know serum levels because we don't know how much scalp DHT comes from body serum and how much is locally produced in the scalp. The scalp has about 1/200th the volume of the body, based on 400 cm3 of scalp vs 80kg of body. male pattern baldness area is 200cm3. So 1 capsule in minoxidil applied over 30 days would give the scalp the equivalent of 0.5*200/30 = 3.33 mg oral, while the body gets 0.5/30 = 0.017 mg of used dutasteride/scalpR5 complex for less side effects. Only 60% is absorbed in the intestine, and probably only 1/5 would penitrate the scalp. The question is how fast would the blood in the scalp rinse away the dutasteride. The worse a man's scalp circulation, the longer it stays there for him. I think 2-4 capsules in 1 minoxidil bottle would do fine. Apply 2 times a day, or use 2% 3 times for a more even dose. The concentration of dutasteride in the bottle is so much lower than that of the minoxidil that I'm sure it will almost all go in.
This is MUCH cheaper than 30 capsules a month, so buy the real Avodart at Walgreens in person and know you are getting real dutasteride.
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Re: Here are my calculations
How do you know?
I wouldn't speculate at all about topical dutasteride until it's actually been tested in vivo. Topical finasteride has had a checkered history of its own, with very mixed results.
What do you mean by "R5"?
A whole lot of speculation in there! :wink:
Bryan
collegechemistrystudent said:
How do you know?
collegechemistrystudent said:
I wouldn't speculate at all about topical dutasteride until it's actually been tested in vivo. Topical finasteride has had a checkered history of its own, with very mixed results.
collegechemistrystudent said:
What do you mean by "R5"?
collegechemistrystudent said:
A whole lot of speculation in there! :wink:
Bryan
Old Baldy
Senior Member
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Bryan: Based on what's in the dutasteride. capsules it appears College is correct in his stability in minoxidil. conclusion? You'd probably want to make 30 day batches at a time?
I'm obviously not sure on this but it seems correct.
It seems to me that emptying 3 dutasteride. gelcaps into a bottle of minoxidil. would do WAY better than mixing with aloe. From all I've read College seems to be on "target" with the major points of his post IMHO.
Also, with dutasteride's large molecular weight, coupled with it being insoluble in water, it seems his advice on making lipid concoctions is correct also?
When I read all the posts about Double A, I wondered why don't those guys just mix 3 gelcaps into a bottle of minoxidil. So maybe I'm biased towards College's advice.
Your statement on whether topical dutasteride. works is a very good one. I certainly don't know. My guess is - yes. Don't ask me how though!
Oh heck, it probably works a little systemically and a little locally. Wow, I really went out on a limb with that one didn't I!?!?
http://www.rxlist.com/cgi/generic3/duagen.htm Btw, the molecular weight of dutasteride. is around 500 if I remember correctly?
College: What is R5? Is this 5AR?
I'm obviously not sure on this but it seems correct.
It seems to me that emptying 3 dutasteride. gelcaps into a bottle of minoxidil. would do WAY better than mixing with aloe. From all I've read College seems to be on "target" with the major points of his post IMHO.
Also, with dutasteride's large molecular weight, coupled with it being insoluble in water, it seems his advice on making lipid concoctions is correct also?
When I read all the posts about Double A, I wondered why don't those guys just mix 3 gelcaps into a bottle of minoxidil. So maybe I'm biased towards College's advice.
Your statement on whether topical dutasteride. works is a very good one. I certainly don't know. My guess is - yes. Don't ask me how though!
Oh heck, it probably works a little systemically and a little locally. Wow, I really went out on a limb with that one didn't I!?!?
http://www.rxlist.com/cgi/generic3/duagen.htm Btw, the molecular weight of dutasteride. is around 500 if I remember correctly?
College: What is R5? Is this 5AR?
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Old Baldy said:
I assumed from what he said that he had found a source saying that dutasteride is compatible with minoxidil. If that's correct, I'd like to see the reference!
Old Baldy said:
Yes. I think trying to mix dutasteride into aloe is a terrible idea. Mixing it into a topical minoxidil solution seems much more feasible.
Old Baldy said:
You bet.
Bryan
Let me clarify
By R5, I meant both enzyemes that turn testosterone into DHT by adding that hydrongen to the double bond.
I did not find a source that says it is stable in minoxidil. I just just looked at the MSDS (every company that carries it, especially in bulk, must have one, and many publish online):
http://redpoll.pharmacy.ualberta.ca/dru ... D00385.txt
http://www.seqchem.com/safetysheet.php? ... =SRP05100d
These two are kind of crappy. I found better ones that listed some stuff it is stable in or not stable in. Just type MSDS Dutasteride into google.
Want to know why topical fiansteride did not work? Because the people who compounded it probably were not real chemists. Any chemist knows that grinding up 25 pills into a paste (I forgot what they wetted it with, a little minoxidil?) and putting it on your skin will not work. First off, only the finasteride in contact with your skin is absorbed, and poorly because it is absorbed better in liquid. Second...
OK, first a lesson in diffusion. Get some food coloring, or even easier, so milk, and put a few drops in water and see hour fast it diffuses. Now put some oil based colloring in vegtable oil. Finally, put some milk (or better, grape juice, on top of a pile of hair gel. That is right: the speed of diffusion was fastest with the first and slowest with the last. Why? Because if the diffusion forces are about the same, then the only factor affecting diffusion rate is the thinkness, which slows the molecules down. Imangine how slow that finasteride must be moving through a paste! It will dry up before more than 1% touches your skin.
Finishing my last sentence, that is why they had poor absorption.
But there was another problem. Finasteride only attacks type II AR5, if that is the short hand (no, I'm not writing out the full name, I think you know what I'm talking about). I'm strongly believe that type I in the skin right next to the follicle produces enough DHT to diffuse over to the follicle and give it DHT that the finasteride can't stop. This diffusion is how newly grafted hairs get their blood. The scalp has many tiny vessels that go in every direction and feed everything, for a transplant surgeon's point of view.
I did read on
http://www.regrowth.com/hairloss-remedy ... esults.cfm
or somewhere like it that a research concluded that most of the DHT in the scalp comes from type I. Unfortunately, because the testes have so much enzyme and testosterone, if you take it orally, dutasteride will get used there first because it likes type II much more than type I. In fact, I saw a graph that showed that Dutasteride will drop DHT levels from type II by 80% before it even starts to touch the type I.
If you want an in vivo test, which I agree on, have your doctor test your dutasteride serum and scalp levels 1, 3, and 11 hours after your application of the minoxidil. Or if that is impractical for one person, we can each pick one of the three and report back. It would be nice to have a base line. I'm not advising anyone to get off Duta for 6 months for a test, but I think the levels from oral uptake would be an OK comparison to the purely topical. Is that in vivo enough for you? You can also have them do a DHT test. The only reason they will turn you down is if you tell them you want the test to know if you are going bald. They will say, "it is not how much DHT you have, but how sensitive your follicles are." You just want to know if it is getting absorbed and how much where and how the DHT is dropping. Do you have volunteers for the 1 hour, 3, and 11 who will take two test, one orally and one later after stopping oral and using topical a planned, recorded time before the test?
By R5, I meant both enzyemes that turn testosterone into DHT by adding that hydrongen to the double bond.
I did not find a source that says it is stable in minoxidil. I just just looked at the MSDS (every company that carries it, especially in bulk, must have one, and many publish online):
http://redpoll.pharmacy.ualberta.ca/dru ... D00385.txt
http://www.seqchem.com/safetysheet.php? ... =SRP05100d
These two are kind of crappy. I found better ones that listed some stuff it is stable in or not stable in. Just type MSDS Dutasteride into google.
Want to know why topical fiansteride did not work? Because the people who compounded it probably were not real chemists. Any chemist knows that grinding up 25 pills into a paste (I forgot what they wetted it with, a little minoxidil?) and putting it on your skin will not work. First off, only the finasteride in contact with your skin is absorbed, and poorly because it is absorbed better in liquid. Second...
OK, first a lesson in diffusion. Get some food coloring, or even easier, so milk, and put a few drops in water and see hour fast it diffuses. Now put some oil based colloring in vegtable oil. Finally, put some milk (or better, grape juice, on top of a pile of hair gel. That is right: the speed of diffusion was fastest with the first and slowest with the last. Why? Because if the diffusion forces are about the same, then the only factor affecting diffusion rate is the thinkness, which slows the molecules down. Imangine how slow that finasteride must be moving through a paste! It will dry up before more than 1% touches your skin.
Finishing my last sentence, that is why they had poor absorption.
But there was another problem. Finasteride only attacks type II AR5, if that is the short hand (no, I'm not writing out the full name, I think you know what I'm talking about). I'm strongly believe that type I in the skin right next to the follicle produces enough DHT to diffuse over to the follicle and give it DHT that the finasteride can't stop. This diffusion is how newly grafted hairs get their blood. The scalp has many tiny vessels that go in every direction and feed everything, for a transplant surgeon's point of view.
I did read on
http://www.regrowth.com/hairloss-remedy ... esults.cfm
or somewhere like it that a research concluded that most of the DHT in the scalp comes from type I. Unfortunately, because the testes have so much enzyme and testosterone, if you take it orally, dutasteride will get used there first because it likes type II much more than type I. In fact, I saw a graph that showed that Dutasteride will drop DHT levels from type II by 80% before it even starts to touch the type I.
If you want an in vivo test, which I agree on, have your doctor test your dutasteride serum and scalp levels 1, 3, and 11 hours after your application of the minoxidil. Or if that is impractical for one person, we can each pick one of the three and report back. It would be nice to have a base line. I'm not advising anyone to get off Duta for 6 months for a test, but I think the levels from oral uptake would be an OK comparison to the purely topical. Is that in vivo enough for you? You can also have them do a DHT test. The only reason they will turn you down is if you tell them you want the test to know if you are going bald. They will say, "it is not how much DHT you have, but how sensitive your follicles are." You just want to know if it is getting absorbed and how much where and how the DHT is dropping. Do you have volunteers for the 1 hour, 3, and 11 who will take two test, one orally and one later after stopping oral and using topical a planned, recorded time before the test?
diffusion
My example diffusions involved color into the solution. I realize if you mix a powder, the finasteride is already mixed. My point is that once the finasteride in contact with the skin entered the skin (if it did in a non-liquid form) then diffusion of finasteride from the rest of the paste to the skin surface would be VERY slow. It would not even move. You'd have better luck with some kind of gel, but I doubt red hair gel will mix with blue if you just squirt one on top of the other. If you really want the slow route, maybe try dissolving some veg oil into the minoxidil to slow evaporation. I looked up the inactive ingredients of minoxidil and avodart and looked up each's MSDS and they are all compatible, chemically and physically. The reason fluridil evaporates so fast is it is pure isoproply alcohol. It would last 30 minutes if they'd add some propylene glycol, which has a boiling point of 119 degrees C. I don't know how enough is absorbed in 2 minutes, but I guess enough is. I'll cut mine though to guarantee absorption.
My example diffusions involved color into the solution. I realize if you mix a powder, the finasteride is already mixed. My point is that once the finasteride in contact with the skin entered the skin (if it did in a non-liquid form) then diffusion of finasteride from the rest of the paste to the skin surface would be VERY slow. It would not even move. You'd have better luck with some kind of gel, but I doubt red hair gel will mix with blue if you just squirt one on top of the other. If you really want the slow route, maybe try dissolving some veg oil into the minoxidil to slow evaporation. I looked up the inactive ingredients of minoxidil and avodart and looked up each's MSDS and they are all compatible, chemically and physically. The reason fluridil evaporates so fast is it is pure isoproply alcohol. It would last 30 minutes if they'd add some propylene glycol, which has a boiling point of 119 degrees C. I don't know how enough is absorbed in 2 minutes, but I guess enough is. I'll cut mine though to guarantee absorption.
dutasteride stability in Rogaine
OK, the MSDS said it is stable in all the active ingredients, except it did not say water. It just said no strong oxidizers. But it is stable in blood, and we can get a blood test. I'd even put in on half my scalp and test both sides to see how fast it diffuses, or put in on one side an hour before and the other side 4 hours before. How much would the test cost? $80? You'd know what you need to know now instead of 7 months from now.
If you are worried about it breaking down in Rogaine in less than a month (half life in the body is 5 weeks due to the liver metabolism), just take an empty bottle of Rogaine, pour 1/4 in from a new bottle, and squirt one capsil in the 1/4 full bottle, then use it in a week and refill.
I'll get a plane ticket and fly to california if someone knows a friendly doctor there. The two I asked so far are affraid of getting sued.
I posted many messages on these boards. Do a member search on me if you want to see what else I wrote.
OK, the MSDS said it is stable in all the active ingredients, except it did not say water. It just said no strong oxidizers. But it is stable in blood, and we can get a blood test. I'd even put in on half my scalp and test both sides to see how fast it diffuses, or put in on one side an hour before and the other side 4 hours before. How much would the test cost? $80? You'd know what you need to know now instead of 7 months from now.
If you are worried about it breaking down in Rogaine in less than a month (half life in the body is 5 weeks due to the liver metabolism), just take an empty bottle of Rogaine, pour 1/4 in from a new bottle, and squirt one capsil in the 1/4 full bottle, then use it in a week and refill.
I'll get a plane ticket and fly to california if someone knows a friendly doctor there. The two I asked so far are affraid of getting sued.
I posted many messages on these boards. Do a member search on me if you want to see what else I wrote.
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Re: Let me clarify
Ok. In that case, what you said earlier was incorrect. Both dutasteride AND finasteride are irreversible inhibitors of the 5a-reductase type 2 enzyme. Dutasteride is NOT an irreversible inhibitor of the type 1 enzyme.
Then it's ironic, isn't it, that the study that tested topical finasteride using a CREAM vehicle was apparently the most successful one? The ones using alcoholic solutions weren't as effective.
The problem with that theory is that tests in both humans and stumptailed macaques have shown that specific 5a-reductase type 1 inhibitors had no noticeable effect on balding. I think it's pretty clear that the type 2 form of the enzyme is much more closely associated with balding than the type 1 enzyme.
Yes, I agree: most of the DHT in scalp _does_ come from type 1. But that's not saying very much! We should be more specifically concerned with HAIR FOLLICLES, as opposed to the entire scalp, which includes lots of other structures like sebaceous glands and sweat glands. The rich supply of the type 1 enzyme in sebaceous glands is misleading, in my opinion, and has little to do with what happens in hair follicles.
That's not because it "gets used there first", it's because it's considerably more potent against the type 2 enzyme than it is against the type 1 enzyme, so dutasteride levels have to build-up higher before they start to inhibit the type 1 enzyme significantly. Furthermore, the type 1 enzyme is produced in cells more rapidly than the type 2 enzyme, resulting in even more of the enzyme that needs to be inhibited.
Bryan
collegechemistrystudent said:
Ok. In that case, what you said earlier was incorrect. Both dutasteride AND finasteride are irreversible inhibitors of the 5a-reductase type 2 enzyme. Dutasteride is NOT an irreversible inhibitor of the type 1 enzyme.
collegechemistrystudent said:
Then it's ironic, isn't it, that the study that tested topical finasteride using a CREAM vehicle was apparently the most successful one? The ones using alcoholic solutions weren't as effective.
collegechemistrystudent said:
The problem with that theory is that tests in both humans and stumptailed macaques have shown that specific 5a-reductase type 1 inhibitors had no noticeable effect on balding. I think it's pretty clear that the type 2 form of the enzyme is much more closely associated with balding than the type 1 enzyme.
collegechemistrystudent said:
Yes, I agree: most of the DHT in scalp _does_ come from type 1. But that's not saying very much!
We should be more specifically concerned with HAIR FOLLICLES, as opposed to the entire scalp, which includes lots of other structures like sebaceous glands and sweat glands. The rich supply of the type 1 enzyme in sebaceous glands is misleading, in my opinion, and has little to do with what happens in hair follicles.collegechemistrystudent said:
That's not because it "gets used there first", it's because it's considerably more potent against the type 2 enzyme than it is against the type 1 enzyme, so dutasteride levels have to build-up higher before they start to inhibit the type 1 enzyme significantly. Furthermore, the type 1 enzyme is produced in cells more rapidly than the type 2 enzyme, resulting in even more of the enzyme that needs to be inhibited.
Bryan
Old Baldy
Senior Member
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College: When a cream dries, I'll usually re-liquify (sp?) the medication by applying another liquid medication. I assume it "gets things going" again?
Also, I can make creams that don't dry for many hours. Does that change the delivery of the medication?
Btw, my main penetration enhancers are PPG/glycols, ethanol, oleic acid, glycerin, isopropyl myristate (sp?) and eucalyptus oil. What penetration enhancers do you recommend? Thanks for any info. (Most of us pre-dissolve the medication in some PPG. I also add a little oleic acid and glycerin to the pre-dissolution part of the "recipe".)
Also, what effect does the lipids produced in the scalp have on absorbing creamed medications over time? I've read they help quite a bit.
Alot of professionals believe medications are delivered better with creams than liquids, so I'm a little confused with your anti-cream statements.
Although I do agree that dutasteride. has a fairly large molecular weight. finasteride. is about 370 mw so I assume that's not so prohibitive?
Also, I can make creams that don't dry for many hours. Does that change the delivery of the medication?
Btw, my main penetration enhancers are PPG/glycols, ethanol, oleic acid, glycerin, isopropyl myristate (sp?) and eucalyptus oil. What penetration enhancers do you recommend? Thanks for any info. (Most of us pre-dissolve the medication in some PPG. I also add a little oleic acid and glycerin to the pre-dissolution part of the "recipe".)
Also, what effect does the lipids produced in the scalp have on absorbing creamed medications over time? I've read they help quite a bit.
Alot of professionals believe medications are delivered better with creams than liquids, so I'm a little confused with your anti-cream statements.
Although I do agree that dutasteride. has a fairly large molecular weight. finasteride. is about 370 mw so I assume that's not so prohibitive?
youngndumb
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i want to give this a try. ill put some dutasteride in minoxidil and apply it topically. can i expect any sie effects from this? currently im on the big 3, finasteride is starting to wear off as ive been on for over 2 years. was thinking about switching to dutasteride, but perhaps should give this a go. i was told that by taking dutasteride id need to be on a topical to reduce testesterone in the scalp. would i still need to do this with the topical dutasteride.? please let me know of any precautions, and what i can do to counter act them. this seems safer than internal dutasteride. feedback anyone?
sorry I did not see this post any sooner
for some reason this was not flagged as new.
Anyway, i don't think creams are bad, when they are mostly liquid and have oils in them. i looked at the ingredients of the cream bryan referenced, and it was mostly fluid with oil, and only some petroleum jelly (2% i think). this should not be a problem at all. may main opposition is actually to pastes. some people grind up 25 proscar pills and add just enough fluid to make a paste, got no results in their studies, and concluded that topicals don't work.
i am become very convinced that oils are needed for absorption. oleic acid is good. i don't yet know the concentrations.
If you really want it to go in, squirt a capsule directly on your scalp and then briefly and lightly rub some oleic acid on the spot. the oil will slow evaporation and help with permeability, while the dutasteride will be in high concentration at the surface of the skin. however, this would only get the dutasteride on maybe 3 square inches and would give you a topical dose when it goes systemic. so this defeats the point, but might help someone who just needs a small bald spot taken care of on one part of their head. I'm not going to do it.
I don't think the high molecular weight is an issue. The main problem is that even minoxidil is only absorbed 1.7 - 5% through the skin, if i understood what i read correctly. for this reason, they use 50mg per dose whereas we have only 0.5mg per pill which, which are $2-3.
i currently recommend 4 capsules per month because even if 100% is absorbed, the systemic concentration will not be high enough to affect 5AR1 outside the scalp, and the local concentration will inhibit almost all DHT. However, if only 3% is absorbed, that means 200*4*0.5*0.03/(30*0.60) = 0.666mg is the equvalent daily oral dose from the scalp's perspective, assuming the drug diffuses to 400 cm3 of scalp by the time all cells take their share, and using the fact that 60% of dutasteride is absorbed in the gut. This is not much different than swallowing a 0.5 mg capsule each day, but the systemic effects would be the same as 0.666mg/200 = 0.00333 mg/day orally, and the liver quicky metabolizes dutasteride at these low doses.
And this is with 3% absorption, compared to minoxidils 1.7-5% absorption. This is ballparking, but also remember that the pores are the highway into the skin, and are where most absorption occurs. at the bottom of each pore is a follicle and a sebaceous gland and a sweat gland, so these structures would get first shot at the dose. From interpreting the graphs bryan has shown me, 2/3 of dht that will enter the cells does enter them in the first hour of dht entering the blood. i also know that 75% of minoxidil that is will be absorbed is absorbed in the first 2 hours after application. So I think if our dutasteride takes an hour or two or 3 to enter, hour scalp cells, especially those by the pores, will be saturated before the remaining dutasteride is swept away to the liver to be metabolized with little effect.
I think you guys should either add 1-2 mL total of oleic acid, or borage seed oil, or emu oil to your minoxidil, or add the minoxidil first and then put the oil on top. i don't know which is best. THe 1-2mL is based on the 60 in the bottle and the cream brian listed having a total of maybe 6% oils and petroleum. please double check that or i will.
i looked at some other people's posts. only one said he had fantastic results in 10 weeks. the rest were people saying they were starting.
for some reason this was not flagged as new.
Anyway, i don't think creams are bad, when they are mostly liquid and have oils in them. i looked at the ingredients of the cream bryan referenced, and it was mostly fluid with oil, and only some petroleum jelly (2% i think). this should not be a problem at all. may main opposition is actually to pastes. some people grind up 25 proscar pills and add just enough fluid to make a paste, got no results in their studies, and concluded that topicals don't work.
i am become very convinced that oils are needed for absorption. oleic acid is good. i don't yet know the concentrations.
If you really want it to go in, squirt a capsule directly on your scalp and then briefly and lightly rub some oleic acid on the spot. the oil will slow evaporation and help with permeability, while the dutasteride will be in high concentration at the surface of the skin. however, this would only get the dutasteride on maybe 3 square inches and would give you a topical dose when it goes systemic. so this defeats the point, but might help someone who just needs a small bald spot taken care of on one part of their head. I'm not going to do it.
I don't think the high molecular weight is an issue. The main problem is that even minoxidil is only absorbed 1.7 - 5% through the skin, if i understood what i read correctly. for this reason, they use 50mg per dose whereas we have only 0.5mg per pill which, which are $2-3.
i currently recommend 4 capsules per month because even if 100% is absorbed, the systemic concentration will not be high enough to affect 5AR1 outside the scalp, and the local concentration will inhibit almost all DHT. However, if only 3% is absorbed, that means 200*4*0.5*0.03/(30*0.60) = 0.666mg is the equvalent daily oral dose from the scalp's perspective, assuming the drug diffuses to 400 cm3 of scalp by the time all cells take their share, and using the fact that 60% of dutasteride is absorbed in the gut. This is not much different than swallowing a 0.5 mg capsule each day, but the systemic effects would be the same as 0.666mg/200 = 0.00333 mg/day orally, and the liver quicky metabolizes dutasteride at these low doses.
And this is with 3% absorption, compared to minoxidils 1.7-5% absorption. This is ballparking, but also remember that the pores are the highway into the skin, and are where most absorption occurs. at the bottom of each pore is a follicle and a sebaceous gland and a sweat gland, so these structures would get first shot at the dose. From interpreting the graphs bryan has shown me, 2/3 of dht that will enter the cells does enter them in the first hour of dht entering the blood. i also know that 75% of minoxidil that is will be absorbed is absorbed in the first 2 hours after application. So I think if our dutasteride takes an hour or two or 3 to enter, hour scalp cells, especially those by the pores, will be saturated before the remaining dutasteride is swept away to the liver to be metabolized with little effect.
I think you guys should either add 1-2 mL total of oleic acid, or borage seed oil, or emu oil to your minoxidil, or add the minoxidil first and then put the oil on top. i don't know which is best. THe 1-2mL is based on the 60 in the bottle and the cream brian listed having a total of maybe 6% oils and petroleum. please double check that or i will.
i looked at some other people's posts. only one said he had fantastic results in 10 weeks. the rest were people saying they were starting.
more thoughts on vehicles
everywhere we keep hearing about chemicals that make the skin more permeable. i ask, "more permiable to what?". Do they mean to anything, including the alcholol, or do they they just mean to dissolved solids? I hope, and partially suspect the later, since most pharmaceuticals tent to be solids. I still do wonder how we are supposed to get the drugs into our skin, and not get the alcohol into our skin, especially when we need the alcohol to dry up our skin. i must also point out that a hot rag to open pores also can cause them to sweat, causing fluid to go the wrong direction. diffusion can still go against this though, so maybe the wider cannals are worth the flow. Anyway, one thing I like about oils is that if they are the same kind that is in the skin, there will be less irritation, and it will not matter as much if the solvent diffuses. in fact, the alcohol will be more likely to not go into the skin because it will have less osmotic pressure. there is already speculation that old skin and balding skin don't have the right kind of oils that they need, and that the right oils can fight hair loss by replenishing this. The higher the concentration of dutasteride in the oil compared to the skin, the higher the osmotic gradient is. However, higher concentration usually means drier and less time left, which is why low concentrations fair well. But you can keep it from drying, then better. A problem with solutions that don't evaporate fast is they tend to be very thick. i don't think a light creme is bad, especially dutasteride can follow oils back and forth across the barriers. it is important not to use too much solution though, if it does not evaporate, because osmotic pressure reaches equilibrium when the concentration of dutasteride on both sides of the skin is the same. So when this occurs, if there is a lot of stuff on the surface, and the concentration is the same as it is in the scalp, that means there is a lot of dutasteride left on the surface. However, I doubt you will have nearly as much on the surface as the volume of your scalp. emu oil is perfectly safe to rub into the scalp. i think rubbing helps it mix into the pours. however, i doubt emu oil is the only good oil. I heard rubbing minoxidil increases absorption. i'm worried though about how much this inceases the absorption of the alcohol.
everywhere we keep hearing about chemicals that make the skin more permeable. i ask, "more permiable to what?". Do they mean to anything, including the alcholol, or do they they just mean to dissolved solids? I hope, and partially suspect the later, since most pharmaceuticals tent to be solids. I still do wonder how we are supposed to get the drugs into our skin, and not get the alcohol into our skin, especially when we need the alcohol to dry up our skin. i must also point out that a hot rag to open pores also can cause them to sweat, causing fluid to go the wrong direction. diffusion can still go against this though, so maybe the wider cannals are worth the flow. Anyway, one thing I like about oils is that if they are the same kind that is in the skin, there will be less irritation, and it will not matter as much if the solvent diffuses. in fact, the alcohol will be more likely to not go into the skin because it will have less osmotic pressure. there is already speculation that old skin and balding skin don't have the right kind of oils that they need, and that the right oils can fight hair loss by replenishing this. The higher the concentration of dutasteride in the oil compared to the skin, the higher the osmotic gradient is. However, higher concentration usually means drier and less time left, which is why low concentrations fair well. But you can keep it from drying, then better. A problem with solutions that don't evaporate fast is they tend to be very thick. i don't think a light creme is bad, especially dutasteride can follow oils back and forth across the barriers. it is important not to use too much solution though, if it does not evaporate, because osmotic pressure reaches equilibrium when the concentration of dutasteride on both sides of the skin is the same. So when this occurs, if there is a lot of stuff on the surface, and the concentration is the same as it is in the scalp, that means there is a lot of dutasteride left on the surface. However, I doubt you will have nearly as much on the surface as the volume of your scalp. emu oil is perfectly safe to rub into the scalp. i think rubbing helps it mix into the pours. however, i doubt emu oil is the only good oil. I heard rubbing minoxidil increases absorption. i'm worried though about how much this inceases the absorption of the alcohol.
more input on vehicles
everywhere we keep hearing about chemicals that make the skin more permeable. i ask, "more permiable to what?". Do they mean to anything, including the alcholol, or do they they just mean to dissolved solids? I hope, and partially suspect the later, since most pharmaceuticals tent to be solids. I still do wonder how we are supposed to get the drugs into our skin, and not get the alcohol into our skin, especially when we need the alcohol to dry up our skin. i must also point out that a hot rag to open pores also can cause them to sweat, causing fluid to go the wrong direction. diffusion can still go against this though, so maybe the wider cannals are worth the flow. Anyway, one thing I like about oils is that if they are the same kind that is in the skin, there will be less irritation, and it will not matter as much if the solvent diffuses. in fact, the alcohol will be more likely to not go into the skin because it will have less osmotic pressure. there is already speculation that old skin and balding skin don't have the right kind of oils that they need, and that the right oils can fight hair loss by replenishing this. The higher the concentration of dutasteride in the oil compared to the skin, the higher the osmotic gradient is. However, higher concentration usually means drier and less time left, which is why low concentrations fair well. But you can keep it from drying, then better. A problem with solutions that don't evaporate fast is they tend to be very thick. i don't think a light creme is bad, especially dutasteride can follow oils back and forth across the barriers. it is important not to use too much solution though, if it does not evaporate, because osmotic pressure reaches equilibrium when the concentration of dutasteride on both sides of the skin is the same. So when this occurs, if there is a lot of stuff on the surface, and the concentration is the same as it is in the scalp, that means there is a lot of dutasteride left on the surface. However, I doubt you will have nearly as much on the surface as the volume of your scalp. emu oil is perfectly safe to rub into the scalp. i think rubbing helps it mix into the pours. however, i doubt emu oil is the only good oil. I heard rubbing minoxidil increases absorption. i'm worried though about how much this inceases the absorption of the alcohol.
everywhere we keep hearing about chemicals that make the skin more permeable. i ask, "more permiable to what?". Do they mean to anything, including the alcholol, or do they they just mean to dissolved solids? I hope, and partially suspect the later, since most pharmaceuticals tent to be solids. I still do wonder how we are supposed to get the drugs into our skin, and not get the alcohol into our skin, especially when we need the alcohol to dry up our skin. i must also point out that a hot rag to open pores also can cause them to sweat, causing fluid to go the wrong direction. diffusion can still go against this though, so maybe the wider cannals are worth the flow. Anyway, one thing I like about oils is that if they are the same kind that is in the skin, there will be less irritation, and it will not matter as much if the solvent diffuses. in fact, the alcohol will be more likely to not go into the skin because it will have less osmotic pressure. there is already speculation that old skin and balding skin don't have the right kind of oils that they need, and that the right oils can fight hair loss by replenishing this. The higher the concentration of dutasteride in the oil compared to the skin, the higher the osmotic gradient is. However, higher concentration usually means drier and less time left, which is why low concentrations fair well. But you can keep it from drying, then better. A problem with solutions that don't evaporate fast is they tend to be very thick. i don't think a light creme is bad, especially dutasteride can follow oils back and forth across the barriers. it is important not to use too much solution though, if it does not evaporate, because osmotic pressure reaches equilibrium when the concentration of dutasteride on both sides of the skin is the same. So when this occurs, if there is a lot of stuff on the surface, and the concentration is the same as it is in the scalp, that means there is a lot of dutasteride left on the surface. However, I doubt you will have nearly as much on the surface as the volume of your scalp. emu oil is perfectly safe to rub into the scalp. i think rubbing helps it mix into the pours. however, i doubt emu oil is the only good oil. I heard rubbing minoxidil increases absorption. i'm worried though about how much this inceases the absorption of the alcohol.
ok, here is the vehicle break down
Currently, topicals specialists are using acids and other agents to make the skin more permeable. I don't like that because it makes it more permeable to everything, perhaps. I prefer to just facilitate the entrance of the active ingredients, not the alcohol as well.
In order for dutasteride to enter the skin, it must be extracted out of its solvent into the skin. For those of you who never took organic chemistry, let me explain something that is critical to designing a delivery vehicle for drugs. This is analogy, with dutasteride being the alcohol, water being the vehicle, and the fats and fluids inside your skin being the ether.
Lets suppose you want to get pure isopropyl alcohol from 70% alcohol / 30% water. Of course you could do fractional distillation (expensive) but you can't do that on your skin. One way to get it out is to extract the alcohol with ether. Ether does not mix with water, but it does mix with alcohol. You pour the ether in to the 70%, and you will see the either floating on top. You cap it, shake it (can't do this with you skin, but bare with me), and let it settle. Again, the ether is on top of the water. Some alcohol is in each layer. You pipette off the ether into another vial, hold it in your hand, and let your body heat boil the ether. You are then left with almost pure isopropyl alcohol. You can repeat this extraction to get more and more isopropyl alcohol out of the water. The faction of alcohol in each later is determined by alcohol's solubility in each layer and the size of the layers. For this reason, you want a vehicle that is much thinner than your skin, and that dutasteride is not super soluble in. So pure ethanol is bad. Dutasteride needs to be soluble enough that it does not precipitate soon as the liquid evaporates. The liquid must evaporate slowly enough that dutasteride has time to enter, but fast enough that the volume of the liquid decreases so that the concentration of Dutasteride outside does not decrease too fast, because the osmotic gradient is driven by the greater concentration of dutasteride on the outside than inside the skin.
Since dutasteride is not water soluble, almost no vehicle that dissolves dutasteride will dissolve it worse than the skin does, so we must accept that less than 100% will go through. But because the skin is so much bigger than than the thin film, it can theoretically still absorb more than 50% of the dutasteride even with its lower concentration just because it has more volume. We just need to help it by making the outside not like dutasteride too much. If your solution dries up, be careful about adding more solvent. If you add more solvent, you will drop the outside concentration of dutasteride, and may extract dutasteride back out of the skin, just like ethanol extracts oils.
Dutasteride solubility is 0mg/mL in water, 44 in ethanol, 64mg/mL in methanol, and 4mg/mL in polyethylene glycol. It comes in glycerol, and I suspect the capsule is 0.15mL. Since it holds 0.5mg, that means the solubility is at least 3.3 mg/mL in glycerol. I don't know the solubility in various fatty acids. Since we will have 4 to 30 0.5 mg capsules in 60mL if rogaine, it should be soluble. However, the minoxidil will compete for solubility, especially at the 5%, since minoxidil is has 7.5% solubility in propylene glycol and only about 3% solubility in ethanol. It is probably close to maxed, buy the dutasteride has opposite solubility ratios (prefers the ethanol) and is already dissolved in glycerol, which minoxidil is very soluble in. 40mg/mL is 4% solubility
I am a bit bothered by putting alcohol on my skin and it getting absorbed. This is necessary though for the active ingredients. Rubbing oils into the skin actually helps hair loss slightly, according to studies. Since emu oil is only 20% better than corn oil, and several other oils, work too, including the fatty acids of saw palmetto, I think the fatty acids have something to do with it. Also, since the skin has oil in it, adding oil to the rogaine will make the outside solubility a little closer to the inside solubility. I suspect that borage seed oil will be the best. This would also dilute the alcohol slightly, reducing the osmotic pressure that pushes skin oils out into the alcohol, and leaving your skin more less dry. This lack mixing could slow the dutasteride's path down the follicle, as well as increase viscosity to slow it. But i read that creams can work well in some cases, and I think adding 1 mL of oil to each 60 mL bottle might help. Check the viscosity of various oils. While I'm guessing flax or borage are best at serving other functions simultaneously, you should pick an oil that has the lowest viscosity and won't clog your pores. Emu is good for the latter, though I don't know the viscosity. At $8 for two ounces, I would avoid emu oil.
Since only about 2% of minoxidil is absorbed through the skin, we might not get better results from dutasteride. But even at this rate, 4 capsules per month would give our scalp the same dose as 1 capsule orally per day would, but it would be so diluted when it reached the body that it would not have much affect at all on serum DHT, or stay in the system long. Now if we can get 10%, absorbed, then we would really knock out the DHT in our scalp. But at 4 capsules per month, it is so cheap that who can complain? Use 10 perhaps.
Currently, topicals specialists are using acids and other agents to make the skin more permeable. I don't like that because it makes it more permeable to everything, perhaps. I prefer to just facilitate the entrance of the active ingredients, not the alcohol as well.
In order for dutasteride to enter the skin, it must be extracted out of its solvent into the skin. For those of you who never took organic chemistry, let me explain something that is critical to designing a delivery vehicle for drugs. This is analogy, with dutasteride being the alcohol, water being the vehicle, and the fats and fluids inside your skin being the ether.
Lets suppose you want to get pure isopropyl alcohol from 70% alcohol / 30% water. Of course you could do fractional distillation (expensive) but you can't do that on your skin. One way to get it out is to extract the alcohol with ether. Ether does not mix with water, but it does mix with alcohol. You pour the ether in to the 70%, and you will see the either floating on top. You cap it, shake it (can't do this with you skin, but bare with me), and let it settle. Again, the ether is on top of the water. Some alcohol is in each layer. You pipette off the ether into another vial, hold it in your hand, and let your body heat boil the ether. You are then left with almost pure isopropyl alcohol. You can repeat this extraction to get more and more isopropyl alcohol out of the water. The faction of alcohol in each later is determined by alcohol's solubility in each layer and the size of the layers. For this reason, you want a vehicle that is much thinner than your skin, and that dutasteride is not super soluble in. So pure ethanol is bad. Dutasteride needs to be soluble enough that it does not precipitate soon as the liquid evaporates. The liquid must evaporate slowly enough that dutasteride has time to enter, but fast enough that the volume of the liquid decreases so that the concentration of Dutasteride outside does not decrease too fast, because the osmotic gradient is driven by the greater concentration of dutasteride on the outside than inside the skin.
Since dutasteride is not water soluble, almost no vehicle that dissolves dutasteride will dissolve it worse than the skin does, so we must accept that less than 100% will go through. But because the skin is so much bigger than than the thin film, it can theoretically still absorb more than 50% of the dutasteride even with its lower concentration just because it has more volume. We just need to help it by making the outside not like dutasteride too much. If your solution dries up, be careful about adding more solvent. If you add more solvent, you will drop the outside concentration of dutasteride, and may extract dutasteride back out of the skin, just like ethanol extracts oils.
Dutasteride solubility is 0mg/mL in water, 44 in ethanol, 64mg/mL in methanol, and 4mg/mL in polyethylene glycol. It comes in glycerol, and I suspect the capsule is 0.15mL. Since it holds 0.5mg, that means the solubility is at least 3.3 mg/mL in glycerol. I don't know the solubility in various fatty acids. Since we will have 4 to 30 0.5 mg capsules in 60mL if rogaine, it should be soluble. However, the minoxidil will compete for solubility, especially at the 5%, since minoxidil is has 7.5% solubility in propylene glycol and only about 3% solubility in ethanol. It is probably close to maxed, buy the dutasteride has opposite solubility ratios (prefers the ethanol) and is already dissolved in glycerol, which minoxidil is very soluble in. 40mg/mL is 4% solubility
I am a bit bothered by putting alcohol on my skin and it getting absorbed. This is necessary though for the active ingredients. Rubbing oils into the skin actually helps hair loss slightly, according to studies. Since emu oil is only 20% better than corn oil, and several other oils, work too, including the fatty acids of saw palmetto, I think the fatty acids have something to do with it. Also, since the skin has oil in it, adding oil to the rogaine will make the outside solubility a little closer to the inside solubility. I suspect that borage seed oil will be the best. This would also dilute the alcohol slightly, reducing the osmotic pressure that pushes skin oils out into the alcohol, and leaving your skin more less dry. This lack mixing could slow the dutasteride's path down the follicle, as well as increase viscosity to slow it. But i read that creams can work well in some cases, and I think adding 1 mL of oil to each 60 mL bottle might help. Check the viscosity of various oils. While I'm guessing flax or borage are best at serving other functions simultaneously, you should pick an oil that has the lowest viscosity and won't clog your pores. Emu is good for the latter, though I don't know the viscosity. At $8 for two ounces, I would avoid emu oil.
Since only about 2% of minoxidil is absorbed through the skin, we might not get better results from dutasteride. But even at this rate, 4 capsules per month would give our scalp the same dose as 1 capsule orally per day would, but it would be so diluted when it reached the body that it would not have much affect at all on serum DHT, or stay in the system long. Now if we can get 10%, absorbed, then we would really knock out the DHT in our scalp. But at 4 capsules per month, it is so cheap that who can complain? Use 10 perhaps.
youngndumb
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has anyone tried this? does it really work?