How much Steroid is Circulating in the BLood at a given time?

[BBC3]

Here is the math...

Take 1000ng/dl.

I understand that to be nanograms per deciliter.

Nanogram = One Billionth of a gram. Ten to the negative 9th. OR .0000000001
Deciliter = one tenth of a liter... .211 pints, OR 3.38 fluid ounces

How much blood in the body ( I HAVE NO F'CKIN IDEA AS THERE ARE MORE IDIOTIC ANSWERS ON THE NET THAN YOU CAN SHAKE A STICK AT)/ The long and short would appear to be about 10 based on average body size. And varying from 8-12 depending on body size. BUT LETS USE 10 FOR THIS EXAMPLE....

10 pints = 160 ounces.
160 ounces divided by 3.38 = 47 Deciliters.
47 Deciliters( total body blood) x .000.000,1 Grams(1000ng) = .00000047 TOTAL GRAMS OF TEST IN THE BODY at any given "Snapshot measurement". And you injected how much? 250MG. (.25G)

So you put in a quarter of a gram on Monday, and all you can see at any one time is 47 millionths of a gram. Back to my point for TRT purpose. FLOWRATE.....would prove operational for measurement. It would seem there is some considerable turnover going on. When you consider these numbers, you have to wonder how TT measurements as a momentary picture apply at all....!?:drooling:

Someone correct my math if I am missing.....

 

[Bill Roberts]

Hint: my post on the kinetics explains this matter.

You're right, the amount present in the blood at any given moment is quite tiny.

 

[Bigkarch]

I agree

 

[Conciliator]

Someone correct my math if I am missing.....

You can't get mad at me... you asked for it

So you put in a quarter of a gram on Monday, and all you can see at any one time is 47 millionths of a gram

.00000047 is 470 billionths, not 47 millionths. However, because of some other mistakes you made (see below) that's actually the correct answer.

47 Deciliters( total body blood) x .000.000,1 Grams(1000ng) = .00000047 TOTAL GRAMS OF TEST

Your answer of .00000047 is off by a factor of 100 (by two decimal places). First, 47 x .0000001 (the numbers you gave) = .0000047 (5 leading zeros, not 6). The second is that 1000ng is 1mcg or 0.000001 grams (5 leading zeros, not 6 like you used). When you correct both, you get the following: 47 x .000001 = .000047 grams (only 4 leading zeros, not 6) = 47 millionths

This reminds me of one of the quotes I just put up here in that debate thread with Bill, :

Furthermore, at all times most of the drug is either at the absorption site or has been eliminated; little is ever in the body. In fact, during the decline phase, drug is eliminated virtually as fast as it is absorbed. Absorption is now the rate-limiting step.

Still, it's interesting to think that only 47 millionths of a gram of testosterone is still about 98 quadrillion atoms (.000047g / 288.42g/mol = 1.62*10^-7 mol * 6.0221415×10^23 atoms/mol)

 

[Bill Roberts]

I've never seen a person who writes so "authoritatively" and who does have some facts at his disposal who so thoroughly lacks understanding and says such completely wrong things.

Conciliator, for you to have said twice now, deliberately quoting yourself:

Furthermore, at all times most of the drug is either at the absorption site or has been eliminated; little is ever in the body. In fact, during the decline phase, drug is eliminated virtually as fast as it is absorbed. Absorption is now the rate-limiting step.

is simply stunning.

How wrong can anyone be?

When a person injects a gram of testosterone ester, for example, there is a gram in the body. Not the extremely tiny amount. Depending on the particular ester, there might well be 900 mg remaining the next day (if a molar amount equivalent to 100 mg of the ester was excreted.)

The small amount is what is in the BLOOD, not the body.

Large amounts are in the body.

If you want to say that you meant "the rest of the body" other than the injection site, that is still wrong because the drug redistributes throughout the body from the injection site in less time than a single half-life. You ought to go read my post in the other thread explaining this, but this time try learning from it which obviously didn't happen before.

So there is a large amount in the rest of the body, if you claim that that was your distinction.

Your other two statements in that quote are wrong as well.

It is clear that you do not know that steroid esters are redistributed from the absorption site throughout the body rather early in the process.

Virtually everything you have said on this is wrong.

The pharmacokinetics of this have been thoroughly studied and are well known, though clearly not to you.

As already mentioned, if you read my steroid esters article and followed the reference given there (Chaudry and James) you would have the information you need, though given your track record I'm fairly sure you would mis-comprehend it. Still, there it is. It is a well-known matter and there is simply no reason for you to be posting nonsense to the contrary such as you have been doing.

Everyone would be better off if your goal and your efforts were towards learning instead of "debating," because your nonsense-but-technical-sounding posts indeed do wind up providing misinformation to many people who do not have the background to spot your fundamental errors.

It is because you have shown me that your attitude is not one of a person having an open mind who wishes to learn, but that of a stubborn donkey who wants to bray the loudest, and the proven fact that back-and-forths with you are useless, that I will not engage in such with you.

It's a totally different story with people who do have an open mind, as most do. There, back-and-forths can be quite productive. But with you, that's not the case, so it's not going to happen.

 

[Stretch]

Bill....

Why did you edit your post??

Originally you called him a complete fool.

Stand strong! Don't back down!


LOLopcorn:opcorn:

 

[Bill Roberts]

I'm an inveterate re-re-re-re-editor, as Millard could woefully acknowledge.

On reading the post, I decided it wasn't a literally EXACTLY correct statement.

I could have changed to "really quite something of a fool" but hadn't thought of that and instead put in whatever is the case above.

More seriously, I thought that the original version could be taken to have an appearance of partially relying on ad hominem attack. Whereas those are merely commentary, and are not the reason why he is wrong.

 

[Stretch]

I just want to see this scenario continue to develope. I think it is beneficial to the board, as long as the authors are willing to keep the ambiguity to a minimum. I understand this is difficult when dealing with such intellectual matters, colloquial language can only carry a conversation so far.

But the sheer amount of information given through debate CAN BE, IMO, the best way to learn. As long as the concepts can be understood by the less educated board members, like myself, I think this could be a great, informative thread.

 

[Bill Roberts]

After I've already given a perfectly clear and sufficient explanation, I don't see a point in repeating myself to a person who I know is not going to do any differently with the repeat than he did with the first.

As for others reading the thread, if the first explanation was clear and sufficient then there is no point for them in my repeating myself, either.

Now if someone else who does have an open mind has a followup question, that's a different story.

On your general point on values of debates: I agree in general. However I use the word in quotation marks ("debate") with regard to Conciliator because there can be no useful debate with a person who refuses to agree on underlying fundamentals which are understood as correct by every scientist in the field, because of not understanding them, as well as having an "I'm going to win on the Internet" mentality and being hopelessly stubborn. For example, previously he didn't understand binding curves and as a result kept repeating the same wrong arguments incessantly when the point was thoroughly proven from the data and any legitimate debate opponent would have granted it, rather than post endless further techno-babble that could sound legit to many readers but was completely wrong, as he did.

And he doesn't understand the fundamental points here either.

To have a useful debate it's necessary for the parties to have the basics understood. Conciliator does not in these matters.

As for others learning from a thread, which is highly desirable (and is for me the main point): what is wrong with having a clear and sufficient explanation from me and then having Conciliator post whatever he wants? That way you get both positions. I have no problem with letting him "have the last word," as he's obviously insistent upon. It's true that he may post further nonsense that has yet more wrong points in it that I don't respond to, but that's a risk that has to be taken. Actually I think there will be less of it if I don't respond to him more than once. That way he will likely have only one more such post, rather than perhaps 10 or 15.

 

[Stretch]

I understand.

You're right though.

At the very least, he does SOUND as if he knows what he's talking about.

Which many times can make him a dangerous person.

An articulate fool. -- although he would, no doubt, describe you in the same manner.

 

[Bill Roberts]

I understand.

You're right though.

At the very least, he does SOUND as if he knows what he's talking about.

Which many times can make him a dangerous person.

An articulate fool. -- although he would, no doubt, describe you in the same manner.

Which would be fair enough if he wishes to do it, and each can decide for himself, as it should be.

 

[Stretch]

Bill, is there any practical application for the topic at hand??

I mean, he says blood levels decline because absorption is slowed. And you say because the test is being broken down and eliminated.

Why should I care??

There is no debate, obviously, to the fact that blood levels decline, and regardless of you or conciliator being correct, you don't disagree with the rate at which blood levels decline. So why does it matter?

 

[Bill Roberts]

There is no virtually no practical application of the difference between what Conciliator says and what I've written, with regard to steroid use.

Using the method of figuring effective levels by using an ordinary half-life calculation, or making a judgment call on how frequently to inject, in no way depends on any of this.

The exceedingly slight -- too slight for me to bother with myself, and I doubt any user does bother with it, difference is that early behavior of blood levels as a result of an injection is not the same as would be figured in the common way. Instead a double-peak phenomenon can occur and rise to maximal level is not immediate due largely to it taking time for the injection to redistribute from the injection site. When little of that redistribution has yet occurred, absorption from the injection site is indeed limiting and so levels do take some time to rise.

However, neither I nor Conciliator was advocating a model claiming immediate peak levels, so there was no practical difference there, in the sense of a person needing to plan differently than he otherwise would have. We both agree (I think he does anyway, though actually the logical consequence of his argument would be the opposite) that levels do not immediately peak, with shorter chain esters being well-known to peak faster than long-chain esters.

 

[Stretch]

That's what I thought.

Thanks Bill

 

[Bill Roberts]

Sure thing!

 

[Conciliator]

I've never seen a person who writes so "authoritatively" and who does have some facts at his disposal who so thoroughly lacks understanding and says such completely wrong things.

Conciliator, for you to have said twice now, deliberately quoting yourself:

Furthermore, at all times most of the drug is either at the absorption site or has been eliminated; little is ever in the body. In fact, during the decline phase, drug is eliminated virlUally as fast as it is absorbed. Absorption is now the rate-limiting step. Under these circumstances, since the rate of elimination essentially matches the rate of absorption

is simply stunning.

How wrong can anyone be?

Bill, this is getting funny. You mistakenly think that I'm quoting myself. I'm not. If you bothered to followed the link I gave, you'd see (in the middle quote) that this comes from the book Introduction to Pharmacokinetics and Pharmacodynamics: The Quantitative Basis of Drug Therapy. See for yourself here under the heading "Absorption is Rate Limiting". Accordingly, what you're saying is not that I, but that these experts on the topic "so thoroughly lack understanding and say such completely wrong things." That's quite the way to paint yourself as the fool Bill.

And in case you want to try to argue that esterfied steroids in oil depots don't fit this description (a drug with rate-limiting absorption and flip-flop kinetics), let me again post the quote I provided here in the debate thread:

Nandrolone displays so-called flip-flop pharmacokinetics. This means that the ascending phase of the curve represents the disposition of nandrolone, and the descending part of the curve represents the rate-limiting process of release of nandrolone decanoate from the muscle into the general circulation (19). Therefore, the half-life in the descending phase of the curve is an estimate of the absorption half-life rather than the elimination half-life.

And Bill, before you jump the gun and make yourself look even more foolish by saying that I don't know what I'm talking about here, this isn't my quote either. http://jcem.endojournals.org/cgi/content/full/90/5/2624 (It's from recent research) on nandrolone pharmacokinetics.

 

[Conciliator]

If you want to say that you meant "the rest of the body" other than the injection site...

No, that's not what I meant, because it wasn't what I said. It's what the authors of the book on pharmacokinetics meant to say. I don't know if you're playing stupid or what, but when they say "most of the drug is either at the absorption site or has been eliminated; little is ever in the body" they clearly mean little is ever in the body beyond the absorption site where the drug was injected. Conceptually, a depot can be thought of as outside the body, from which the drug is slowly being "absorbed into" the body.

that is still wrong because the drug redistributes throughout the body from the injection site in less time than a single half-life.

No, it's still correct because very little androgen is distributed throughout the body. Only the unbound drug is available for passive diffusion into tissues. And free androgen levels are extremely low. Second, research such as this explains that the "volume of distribution" for nandrolone and testosterone is a mere 10-20 liters. By definition of "volume of distribution" we can calculate the total amount of drug in the body. Assume a serum free test level of 100 pg/ml, which is consistent with a total test level of 1000 ng/dl. 100 pg/ml = 100 ng/L. Multiply that by the volume of distribution of 20 (the high end) and you get merely 2 mcg of free testosterone distributed throughout the body. In other terms, assuming 5 liters of actual plasma, the total amount distributed in the body is only around 2-4 times the amount found in the blood. The known volume of distribution for nandrolone and testosterone clearly contradict your claim that there's significant distribution in the body. The fact is that most of the drug is either at the injection site or has been eliminated, just like the quote said. You really don't know what you're talking about Bill.

Your other two statements in that quote are wrong as well.

The other two statements are correct, and all the other quotes I've provided support them. For example, one of those statements is that "Absorption is now the rate-limiting step." You say that's wrong. But look at the paper on nandrolone that I quoted above which states that "the descending part of the curve represents the rate-limiting process of release of nandrolone decanoate from the muscle into the general circulation (19). Therefore, the half-life in the descending phase of the curve is an estimate of the absorption half-life rather than the elimination half-life. " And look at the other references in the debate thread. One states that "For orally administered drugs, the rate-limiting step is metabolism, whereas for depot agents it is their rate of absorption." Another one states that for "Intramuscular depot injection," the rate of absorption is rate limiting and the rate constants ka and k appear to have been exchanged -- this is sometimes referred to 'flip-flop' kinetics." How on earth, in light of all this, are the authors of the book on pharamacokinetics wrong to say that "Absorption is now the rate-limiting step."? Seriously? Answer the question.

I don't see how you so obstinately continue to assert that I'm wrong and you're right when reference after reference and quote after quote contradicts you and supports exactly what I'm saying. Do you not realize that I've now provided 9 references (8 before and the 1 here on the volume of distribution) and you've provided zero? It's not your word against mine. It's your word against all the texts on pharamacokinetics that I've quoted for everyone to see.

 

[BBC3]

Originally Posted by Bill Roberts
If you want to say that you meant "the rest of the body" other than the injection site...

No, that's not what I meant, because it wasn't what I said. It's what the authors of the book on pharmacokinetics meant to say. I don't know if you're playing stupid or what, but when they say "most of the drug is either at the absorption site or has been eliminated; little is ever in the body" they clearly mean little is ever in the body beyond the absorption site where the drug was injected. Conceptually, a depot can be thought of as outside the body, from which the drug is slowly being "absorbed into" the body.

Conci, I find it rather amusing to see you look for shelter in ambiguosity as above. Thats twice I have seen you resort that in these days.... Especially funny as you seem find so much error in my use of "terminology"...

Quote:
Originally Posted by Bill Roberts
that is still wrong because the drug redistributes throughout the body from the injection site in less time than a single half-life.

When I first read this I am wondering if Bill is giving merit to my thoughts that esterfied steroid can redistribute to distant fat and find shelter prior to metabolism.......?

I also find it interesting in that it was Conci, who posted that article on the Deca that stated the 100, or 150mg injection reached peak concerntration within close to a week???

Finally, and at a minimum, ALL BILL SAID was that you could find steroid throughout the body within a week!! NOTHING MORE. He did not put any boundaries, requisits, or minimums applying.!!!!

I have argued with you in the past and felt as if I were banging my head on a wall. At least now I have a witness!!!

Conci, communication with you is DIFFICULT. I cant help but think you know what you are doing and that it is an attempt to create a simple mis-step from you opponent of the moment. It appears to be incideous twisting.......... No one can be this far off in communication. It is borderline SCHIZO BEHAVIOR!!!!!


No, it's still correct because very little androgen is distributed throughout the body. Only the unbound drug is available for passive diffusion into tissues. And free androgen levels are extremely low. Second, research such as this explains that the "volume of distribution" for nandrolone and testosterone is a mere 10-20 liters. By definition of "volume of distribution" we can calculate the total amount of drug in the body. Assume a serum free test level of 100 pg/ml, which is consistent with a total test level of 1000 ng/dl. 100 pg/ml = 100 ng/L. Multiply that by the volume of distribution of 20 (the high end) and you get merely 2 mcg of free testosterone distributed throughout the body. In other terms, assuming 5 liters of actual plasma, the total amount distributed in the body is only around 2-4 times the amount found in the blood. The known volume of distribution for nandrolone and testosterone clearly contradict your claim that there's significant distribution in the body. The fact is that most of the drug is either at the injection site or has been eliminated, just like the quote said. You really don't know what you're talking about Bill.

Quote:
Originally Posted by Bill Roberts
Your other two statements in that quote are wrong as well.

The other two statements are correct, and all the other quotes I've provided support them. For example, one of those statements is that "Absorption is now the rate-limiting step." You say that's wrong. But look at the paper on nandrolone that I quoted above which states that "the descending part of the curve represents the rate-limiting process of release of nandrolone decanoate from the muscle into the general circulation (19). Therefore, the half-life in the descending phase of the curve is an estimate of the absorption half-life rather than the elimination half-life. " And look at the other references in the debate thread. One states that "For orally administered drugs, the rate-limiting step is metabolism, whereas for depot agents it is their rate of absorption." Another one states that for "Intramuscular depot injection," the rate of absorption is rate limiting and the rate constants ka and k appear to have been exchanged -- this is sometimes referred to 'flip-flop' kinetics." How on earth, in light of all this, are the authors of the book on pharamacokinetics wrong to say that "Absorption is now the rate-limiting step."? Seriously? Answer the question.

PLEASE DEFINE ABSORPTION. I am assuming the authors are referring to RE-ABSORPTION INTO THE BLOOD??!?!!? Again, Bill already stated that the long ester was the main hold up??

I don't see how you so obstinately continue to assert that I'm wrong and you're right when reference after reference and quote after quote contradicts you and supports exactly what I'm saying. Do you not realize that I've now provided 9 references (8 before and the 1 here on the volume of distribution) and you've provided zero? It's not your word against mine. It's your word against all the texts on pharamacokinetics that I've quoted for everyone to see.

Again, my understanding was that Bill simply pointed out an error of your thinking and then went on to state what you NEXT posted the 9 references to REINFORCE???? WHAT AM I MISSING??

I can't help but think much of this is miscommunication. CLEARLY, the majority of it is Conci hammering away at the same concept Bill already stated.

Conci, please go back and read the other post when Bill discussed your blood plasma specific gravity/mass limiting factors as they apply in principle, then see where he discussed long chain ester solubility as the primary factor limiting AAS. There appear to have been some misinterpretations of terms like "body" and "metabolism". If I am not mistaken, you may have even been taking them STRICTY in that post, and now USING THEM LOOSELY here!?!?! Proof enough. If you would go back, quote that post, and explain your interpretation step by step, then perhaps he would oblige you once understading your term usage, or misinterpretation. You may even be multiple personality if you cant see it...... You know the post, it was the one you started this based on. I have already explained my apparently correct interpretation of this, to which you have ignored me once already, so that you can continue on this campaign to "jilt" Bill into an error on his part. Until you clarify why you cant see that he stated what you are argueing, you are digging the hole that much deeper..... POOR BATTLE CHOSEN....[]

 

[Conciliator]

BBC3, I've taken the time to address everything you've asked and talked about. Please take the time to read it through and ask questions if something I said doesn't make sense.

Conci, I find it rather amusing to see you look for shelter in ambiguosity as above.

No one is being ambiguous. The quote makes it clear that the absorption site where the drug was injected is being considered separately from the rest of "the body." It's not ambiguous at all. Just read the quote. It makes further sense when you consider that in pharmacokinetics, the "distribution" of a drug throughout the body does not include the depot, as the depot is conceptualized as containing drug that still hasn't been absorbed into the body in the first place.

I also find it interesting in that it was Conci, who posted that article on the Deca that stated the 100, or 150mg injection reached peak concerntration within close to a week???

No, I didn't post that. I think you're confusing the absorption half-life with the time to peak, which are two different pharamacokinetic variables.

Finally, and at a minimum, ALL BILL SAID was that you could find steroid throughout the body within a week!! NOTHING MORE.

But he did say more. He argued that it was because of the distribution that it was wrong to say that "little is ever in the body." However, the volumes of distribution for nandrolone and testosterone are very low, which means at any given time, there IS very little in the body (beyond the depot). There's only a few times more in the body than what's in the blood (which is a tiny amount, as this thread explained in the first place).

PLEASE DEFINE ABSORPTION. I am assuming the authors are referring to RE-ABSORPTION INTO THE BLOOD??!?!!?

It's not re-absorption. The term in pharmacokinetics is just "absorption". In simple terms, it refers to movement of a drug into circulation, whether that be from the stomach, GI tract, skin, a depot, etc. More specifically here, the pharmacokinetic term "absorption" refers to the process in which 1) the esterfied steroid diffuses from the oil depot into the interstitial fluid, 2) esterases in the interstitial fluid rapidly hydrolyze the ester back to the parent steroid, and 3) the parent steroid diffuses into local capillaries and enters circulation. That's what absorption refers to.

Again, Bill already stated that the long ester was the main hold up??
...
I can't help but think much of this is miscommunication. CLEARLY, the majority of it is Conci hammering away at the same concept Bill already stated.

Conci, please go back and read the other post when Bill discussed your blood plasma specific gravity/mass limiting factors as they apply in principle, then see where he discussed long chain ester solubility as the primary factor limiting AAS.

Right, I think we agree that diffusion from the depot (and subsequent de-esterfication) is rate-limiting. However, Bill seems not to understand what "absorption" means in pharmacokinetics. He also seems to not understand that the volume of distribution is very small, that almost all of the drug is either in the depot or already eliminated from the body. I'm not sure if he understands that decline of the drug in serum during the elimination phase reflects the long absorption half-life.

There appear to have been some misinterpretations of terms like "body" and "metabolism". If I am not mistaken, you may have even been taking them STRICTY in that post, and now USING THEM LOOSELY here!?!?! Proof enough.

I didn't use the term metabolism, Bill did. Specifically, he said that I was incorrect to say that metabolism was not rate limiting. But I never used the word metabolism. I said "absorption" was rate limiting, and that term has a defined meaning in pharmacokinetics. I once thought that we just had a disagreement over what "absorption" means, but his last post in this thread demonstrates that there's more.

Again, my understanding was that Bill simply pointed out an error of your thinking and then went on to state what you NEXT posted the 9 references to REINFORCE???? WHAT AM I MISSING??

What error in thinking did he point out? His vague explanation was that what I said "is totally screwed up." Yet all the references say exactly what I said, with the same terms and concepts. How could you think that the references reinforced what he said? They squarely contradicted him, as the emboldened parts of my last post show. The references reinforce what I'm saying, both in terminology and concept.

 

[Conciliator]

...due largely to it taking time for the injection to redistribute from the injection site. When little of that redistribution has yet occurred, absorption from the injection site is indeed limiting and so levels do take some time to rise.

Bill, honest question here. What exactly do you mean when you say "re-distribution"? Are you talking about esterfied steroid being "re-distributed" from the injection site throughout the body, or the base steroid? Perhaps this is where we're not seeing eye to eye, if you think that the still-esterfied steroid gets distributed.