MACRO/ULTER........Testing a new Aromatese Inhibitor Formula:

[macrophage69alpha]

if you were to actually read that study you would realize that its an erroneous finding. Unfortunately in 1986 the aromatase system was not well understood and thus you get findings like this.

Just so that you understand what they are saying, wrong though it is...

is that ATD is a ERB (estrogen receptor blocker)- hence why the term DEFEMINIZATION (not feminization)

subsequent studies with all aromatase inhibitors show different LH response in castrated vs. sham operated animals.

 

[Ulter]

Medical science has come a long way in 20 years Anthony.

There's a study showing that women taking birth control pills shouldn't smoke cigarettes. It was believed that the birth control pills caused cancer in smokers. Later they found it was the cigarettes. You should really check more recent studies when they are available.

 

[Anthony Roberts]

yes and no.

if you had actually done a search on pubmed you would realize that the potency is similar, oral bioavailability is the issue. Hence why its a topical (aka transdermal) formulation.

just to clarify exemestane is not an anti-estrogen, its an aromatase inhibitor-- a suicidal one- the same as ATD.

in point of fact anti-estrogen is a often used misnomer. example nolvadex and clomid are not anti-estrogens they are SERMs.

Transdermal application, however, wouldn't solve that problem, would it?

I mean...from reading the literature included with the testosterone gel and patch (transdermal), it would appear that only about 10% of the active drug makes it through.

I also coulen't find the study where it said oral availability was an issue with this compound. Could you be so kind as to post it, and explain how transdermal application would solve the problem of bioavailability...?

 

[Ulter]

Transdermal application, however, wouldn't solve that problem, would it?

I mean...from reading the literature included with the testosterone gel and patch (transdermal), it would appear that only about 10% of the active drug makes it through.

I also coulen't find the study where it said oral availability was an issue with this compound. Could you be so kind as to post it, and explain how transdermal application would solve the problem of bioavailability...?

It's a good thing we don't use a patch or gel then isn't it?

 

[macrophage69alpha]

I also coulen't find the study where it said oral availability was an issue with this compound. Could you be so kind as to post it, and explain how transdermal application would solve the problem of bioavailability...?

transdermal delivery, with a good vehicle can typically achieve 30-40% delivery delivery that extends over 3-8hrs (lag)- with tissue release that is significantly longer (particularly in lipophillic drugs- steroids). oral bioavailability of non alkylated androgens is typically 2-3% with massive first pass elimination and short half life 20-40minutes. even at 10% delivery thats 3-5 times greater BA.


to answer your question- you did not look and take the above and figure it out.

 

[Anthony Roberts]

transdermal delivery, with a good vehicle can typically achieve 30-40% delivery delivery that extends over 3-8hrs (lag)- with tissue release that is significantly longer (particularly in lipophillic drugs- steroids).
.

My apologies. I still don't get it. It would appear that transdermal gel (testosterone in this case) results in 9-14% bioavailability, in this case. Might I ask where the 30-40% delivery number comes from? Can you please provide a study confirming those numbers regarding this particular AI, instead of giving me keywords to search on PUBMED with? I'm simply not bright enough to dig up the studies confirming the numbers you are providing, with my limited abilities. You're telling me that lipophillic drugs like steroids have that 30-40% absorbtion rates, yet the literature included with every single hormone replacement therapy that is transdermal indicates a 10% or so rate. This is my finding as well as William Llewellyn's, both of whom have written books on anabolics.

I don't understand how I can't find any studies where these claims can be verified...but here;'s one that seems to dispute those claims regarding absorbtion rates...

J Clin Endocrinol Metab. 2000 Dec;85(12):4500-10.


Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men.

Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N.

Divisions of Endocrinology, Departments of Medicine/Pediatrics, Harbor-University of California-Los Angeles Medical Center, Torrance, California 90509, USA.

Transdermal delivery of testosterone (T) represents an effective alternative to injectable androgens. Transdermal T patches normalize serum T levels and reverse the symptoms of androgen deficiency in hypogonadal men. However, the acceptance of the closed system T patches has been limited by skin irritation and/or lack of adherence. T gels have been proposed as delivery modes that minimize these problems. In this study we examined the pharmacokinetic profiles after 1, 30, 90, and 180 days of daily application of 2 doses of T gel (50 and 100 mg T in 5 and 10 g gel, delivering 5 and 10 mg T/day, respectively) and a permeation-enhanced T patch (2 patches delivering 5 mg T/day) in 227 hypogonadal men. This new 1% hydroalcoholic T gel formulation when applied to the upper arms, shoulders, and abdomen dried within a few minutes, and about 9-14% of the T applied was bioavailableCOLOR]. After 90 days of T gel treatment, the dose was titrated up (50 mg to 75 mg) or down (100 mg to 75 mg) if the preapplication serum T levels were outside the normal adult male range. Serum T rose rapidly into the normal adult male range on day 1 with the first T gel or patch application. Our previous study showed that steady state T levels were achieved 48-72 h after first application of the gel. The pharmacokinetic parameters for serum total and free T were very similar on days 30, 90, and 180 in all treatment groups. After repeated daily application of the T formulations for 180 days, the average serum T level over the 24-h sampling period (C(avg)) was highest in the 100 mg T gel group (1.4- and 1.9-fold higher than the C(avg) in the 50 mg T gel and T patch groups, respectively). Mean serum steady state T levels remained stable over the 180 days of T gel application. Upward dose adjustment from T gel 50 to 75 mg/day did not significantly increase the C(avg), whereas downward dose adjustment from 100 to 75 mg/day reduced serum T levels to the normal range for most patients. Serum free T levels paralleled those of serum total T, and the percent free T was not changed with transdermal T preparations. The serum dihydrotestosterone C(avg) rose 1.3-fold above baseline after T patch application, but was more significantly increased by 3.6- and 4.6-fold with T gel 50 and 100 mg/day, respectively, resulting in a small, but significant, increase in the serum dihydrotestosterone/T ratios in the two T gel groups. Serum estradiol rose, and serum LH and FSH levels were suppressed proportionately with serum T in all study groups; serum sex hormone-binding globulin showed small decreases that were significant only in the 100 mg T gel group. We conclude that transdermal T gel application can efficiently and rapidly increase serum T and free T levels in hypogonadal men to within the normal range. Transdermal T gel provided flexibility in dosing with little skin irritation and a low discontinuation rate.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 11134099 [PubMed - indexed for MEDLINE]

 

[TheRide]

Come on Fonz we're waiting. Show us how out of our league we are.

HOLY SHIT!!!!!!!!!!!

Now THERE is a name I haven't heard in a while.... ahhhh this thread is about to get VERY interesting!!!

 

[Ulter]

Come on Anthony your search skills are just fine. If they weren't you wouldn't have been able to put all that information Nandi and Macro have posted in the last 5 years into your book.

Again, it's a good thing we aren't using gel for delivery of this AI. And since I already posted that I'm not sure why you'd post a study about it.

 

[Anthony Roberts]

Come on Anthony your search skills are just fine. If they weren't you wouldn't have been able to put all that information Nandi and Macro have posted in the last 5 years into your book.

Again, it's a good thing we aren't using gel for delivery of this AI. And since I already posted that I'm not sure why you'd post a study about it.

I'll be frank and say that I haven't used anything that macro has ever posted, to my knowledge in my book.

As for Karl (Nandi), my book is dedicated to him, and my correspondance with him was very beneficial to my writings. I didn't have to search to put that information into my book, as I was corresponding with Karl until my second issue writing for the online magazine he wrote for.

I'm sure Macro has contributed quite a bit to the development of several products...however, I concur with Llewellyn when he says Duchaine really developed the first transdermal Yohimbe product, and interestingly, I found that the Sesame product that he has developed appeared elsewhere first....

How odd.

I haven't ever used Macro's research for anything. Unless you're talking about my using those who researched and developed "his" products first (Duchaine, Karl- Nandi, etc...) all of whom have their names in my book's dedication.

 

[Ulter]

It's funny how things get repeated over and over on the boards, end up in a book, and no one knows where they started. But that's the nature of the boards.

I don't think anyone has posted more times than I have that Duchaine pioneered transdermal yohimbine delivery. In fact I just did a search and found my first posts about it in 2002. So you're posting old news, again.
Macro didn't develop a sesamin product first either. I don't think anyone said he did so I'm not sure what your purpose is for posting it.

What you're leaving out though is that although someone else may pioneer an idea, those who come later may find it's flaws and perfect it. Like Macro has with Yohimburn. He also found a better yet less expensive form of sesamin, again perfecting an idea.

Who brought R+ Lipoic Acid to the United States market? Who discovered the need to mix it with biotin? Who is the world largest provider of R+ lipoic acid? And that's only one supp. Anytime you'd like to match accomplishments with us you just let me know the time and place.

You've made a lot of enemies from what I'm told. I consider you a friend of mine, did you want to change that?