We know that after an IM injection of oil-based AAS, there's a sharp peak and then a slow decline. Now, what is causing the decline? What does the decline represent? Is it the body slowly breaking down and eliminating the test that's in circulation? Or is it the test still being absorbed by the body, but at a slower and slower rate?

For most drugs, levels in the body rise as the drug gets absorbed. For example, if you take an oral steroid, the steroid is absorbed from the GI tract fairly quickly. The entire absorption phase takes only a few hours. In other words, all of the oral steroid is digested and ends up in circulation in a matter of hours (in accordance with its bioavailability). As the drug is being absorbed, blood levels get higher and higher until they reach a peak. The phase where blood levels are increasing (until the peak) is called the absorption phase. As we know, the body processes drugs, like the oral steroid. The liver and other enzymes in the body break it down and metabolize it. As that happens, levels in the body decline (from the peak), until essentially all of the oral steroid is gone and there is none in the blood. The phase where blood levels are dropping after the peak is called the elimination phase.

OK. That's a typical case. Based on this model, if we look at test cyp, we might think that levels in the body rise as all of the test enters the body's circulation. We might think that the absorption phase represents all of the test being absorbed into the body. We might also think that decline of the drug, during the elimination phase, is due to the body slowly breaking it down and metabolizing it. This is the important point. Although we might think that and it might appear to be the case, it's NOT.

So what's really happening then? When you inject an steroid, you're creating what's called a "depot" in the muscle. When you inject a steroid and create an "oil depot" in muscle, you're creating what is essentially a steroid storage place. Unlike what we might have thought above, all the steroid does not quickly enter into circulation. It's not quickly absorbed at all. Instead, it stays in the depot. The steroid leaves the depot , enters circulation, and gets absorbed into the body relatively slowly. The longer the ester is, the more slowly it leaves the depot. That's because the depot consists of oil (fat) and the longer the ester is, the more lipophilic, or "fat-loving" it is. An important feature of a depot is that release of the drug follows a half-life. That means the steroid doesn't leave at a constant rate, but it leaves slower and slower as time goes on. For example, if we had a depot containing 200mg of test cyp, the first 100mg might leave the depot and get absorbed into the body in the first 3 days. In the next 3 days, 50mg might leave. In the next 3 days, 25mg might leave. And so on. This would represent a 3-day half-life of absorption. Every 3 days, half of the steroid leaves the depot and gets absorbed by the body.

So what does it represent here when blood levels of the drug decline during the elimination phase? As I said earlier, we might mistakenly believe it's due to the body slowly breaking down and metabolizing all the test we injected. But in fact, it represents absorption of the drug from the depot. The reason blood levels are declining is actually due to the fact that the amount being absorbed by the body is slowly decreasing, due to the half-life I explained above. The decline doesn't represent the rate at which the body is breaking down, or clearing the drug at all, but rather the rate at which it's slowly absorbing it! This is called 'flip-flop' kinetics. What we see in the "elimination phase" (as levels drop from the peak) actually represents not clearance or elimination from the body, but the rate of absorption into the body,

So, suffice it to say "free testosterone" has a very short half life in the serum, because unless it attaches itself to a circulating protein it will enter the cell.

The type of ester determines how long a particular AAS remains in the depot, which is the primary determinant of the AAS half life because once exposed to esterase the anabolic won't be around much longer, perhaps a few hours at best.

Here are a few references for those who like such things.

"Pharmacokinetics of the long-acting depot preparations
The slow release of the active drug contained in depot preparations profoundly affects their pharmacokinetics and they differ from oral drugs in four key respects:
...
2. For orally administered drugs, the rate-limiting step in metabolism, whereas for depot agents it is their rate of absorption. The absorption rate constant for depot drugs may be less than the their elimination rate constant, which is termed a 'flip-flop' pharamacokinetic profile.

P.253
http://www.amazon.com/Seminars-General-Adult-Psychiatry-College/dp/19046...

"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. "

http://jcem.endojournals.org/content/90/5/2624.full

"Variations in side-chain ester chemistry are important in the pharmacokinetics of androgen esters in oil vehicle (Behre et al., 1990). Experimental studies suggest that absorption rates are predicted by the oil/water partition coefficients (or hydrophobicity) and that the oil vehicle is absorbed more slowly than the androgen ester (Tanaka et al., 1974). "

http://jpet.aspetjournals.org/content/281/1/93.full

Table 4 in this last study shows that the absorption half-time of deca injections is much, much longer than the clearance half-time. For example, a 100mg injection in 1ml of oil into the gluteal muscle has an absorption half-time of 7.7 days and a clearance half-time of .34 days. When the delt muscle is used, the absorption half-time is 12 days and the clearance half-time is .25 days.

This is interesting because I have seen several studies that indicate that the absorption half-time when injected into the delt is two to three times that when injected into the glute. The standard half-lives are standardized for the glute. Some feel the quicker absorption is due to exercise, which the glute is exercised just by walking, while the delt obviously is generally worked less.

Also, while these studies indicate what happens after a single injection, we know that something other than that occurs in the real world. I would like to know what happens after repeated injections to a single muscle group. For example:

(1) At what point does the esterfied drug start to saturate into heavy "off-site" adipose tissue. Meaning, at what time does pinning one's right buttock, does the oil begin to leach out toward the fat of his ass. This will prove to be a completely different release rate.

(2) By what means does the esterfied steroid disperse beyond the immediate muscle. Can it travel via blood stream to fat in other areas? Is it only local at best if at all?

(3) If local only, is the time that the ester can move away from the immediate muscle limited to the amount of time the BB will sustain the increased solubility?

(4) Or would excess injections simply saturate immediately into general circulation via capillary action? If so, how do circulating fat levels act in this process, and if if heavy and constant enough, does this provide for a vehicle to travel to peripheral areas elsewhere, muscle or fat.?

(5) I also think that the BB should not be discounted for these purposes. Clearly the role of the BB is to provide for solubility while the injection disperses, so when you begin to deal with this real scenario of saturation of a muscle group, it could perhaps be in play to a larger extent, and depending on its type of bond with the ester. I am suspicious that the BB gives the ester extra ability to enter general circulation from a saturated muscle, especially the first two days it remains effective. Does it? Could it also provide protection in the blood stream to deliver the ester to remote locations?

(6) Clearly muscles will saturate soon after a first few 400mg injections. So what gives?

So as usual, I am left with more questions than answers but hopefully this was educational / interesting / thought-provoking for some of you.

Edit: The main point I wanted to convey here ( for those who want the Cliff-Notes ) is that the half-lives of the various esters are due to the differences in their absorption from the depot. Once the ester is cleaved by esterase enzyme, test is test is test. And that the muscle injected into can greatly affect the half-life as well.