Conciliator.
I'd like to respectfully suggest that you post in VERY PLAIN WORDS, the argument that you are trying to make. This will greatly increase the benefit to the board. Rather than two people arguing over things that the average poster cannot begin to understand. I know I don't understand what the practical application is.
I'll give it a shot. Let's start by looking at a graph of blood levels of testosterone after an injection of 200mg of test cyp.
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Just as newbie said, there's a sharp peak and then a slow decline. The statement I made (and that Bill disagreed with) has to do with the following question: 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 the chart above for 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. In common usage, a depot is a storage place, right? 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,
I think that pretty much sums it up. If there was anything I said or terminology I used that wasn't entirely clear, let me know and I can try to clarify it.
I'll end by quoting what I said one more time. It should hopefully make a lot more sense now:
Usually when people talk about the biological half life, they're referring to the clearance or elimination half life. That's because most drugs are quickly absorbed (usually orally, from the GI tract) and decline of the drug in the body is determined primarily from the elimination or "disposition," which is rate limiting. With intramuscular injections into oil depots, the rate limiting process is not clearance from the body, but absorption into the body. The body essentially eliminates the drug as fast as it's absorbed. Whereas longer esters have an absorption half life of several days to over a week, the clearance half life of the actual hormone is much, much shorter. When the ester is cleaved and the base hormone is released and enters into circulation, it's half life is usually a matter of hours, depending on serum binding. Since the absorption half life is so much longer, decline of the drug in the body corresponds to the absorption half life.
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