SubQ might not doing it for me

[Gianluca]

NEW INSIGHTS INTO DRUG ABSORPTION FROM OIL DEPOTS

This dissertation provides new insights into drug absorption from oil depots. Figure 7.1, which was the assumed model before these new findings, is adapted to Figure 7.2. Here, it is shown that the released prodrug (ND) is not hydrolysed locally (Chapter 6), but remains unchanged in interstitial fluid. Here, it is logical to assume that the lipophilic prodrug adheres to small proteins (<40 kDa) and subsequently drained with the interstitial fluid into the lymph vessels. Alternatively, it cannot be excluded that small oil droplets might be detached from the main oil depot (Chapter 4) and cleared through the lymph. In both ways, ND will end up in the final lymph node to enter the vena cava superior to meet blood cells in the central compartment. These blood cells will finally hydrolyse the prodrug compound to nandrolone

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FUTURE PERSPECTIVES

The open ends of the current research have been indicated above. Both the fate of the oil and the role of the immune system towards drug absorption are still not fully understood. In future research, an option to examine drug release and absorption from an oil depot can be performed with a traceability in vivo study. Ideally, 3 tracers would be integrated in the drug product: 1 in the triglyceride structure of the oil components, 1 in the nandrolone molecule and 1 in the decanoic acid moiety. The distinctiveness between these three tracers and between the tissues must obviously be sufficient enough to determine the three compounds separately. The whole process of drug release, hydrolysis and oil digestion could then be followed. Nowadays, traceability studies can be performed for instance with Single-photon emission computed tomography (SPECT) or PET/MRI-scanners. These imaging techniques use respectively isotopes or fluoride-atoms to visualise compounds in situ. Unfortunately, these labeling materials are unsuitable to use in the suggested traceability study, because these materials will alter the physical-chemical properties of either the oil formulation or the prodrug compound. This may change the oil viscosity, drug partition coefficient, spatial distribution in administered tissue or immune response, which may consequently influence the biopharmaceutical aspects of drug absorption from oil depots when these materials are not applied.








CONCLUSIONS

It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two phase mass transfer model where concentration gradients, diffusion and partition coefficients would enable the calculation of the expected absorption. It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. The oil depot forms a continuous phase after injection, but will be dispersed and encapsulated at the injection site after some days. This in turn largely influence the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolysed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time. This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug. Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.




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this is awesome, but not sure if I'm understanding well.

So the SubQ is absorbed slower but enter the blood faster
the IM is absorbed faster but enter the blood slower?

basically at the end we have same absorption just it is released in the blood in a different way

 

[Cataceous]

Below is a graph from the work referenced by @madman. This give a feel for the kinds of differences you can expect with different injection sites and methods. This is using nandrolone decanoate, and suggests a much longer half-life for subQ. In the Antares study the half-life for subQ T enanthate was about 50% longer than for IM.

 

[Gianluca]

10 pg/mL = 1 ng/dL. So your number is 21.3 ng/dL. I'm not sure why the LabCorp scale is relatively low, so a direct comparison is still questionable.

For calculated free T some labs say 21 ng/dL is around the top of the normal range. Calculated is also nice because you can look at studies for average numbers. For example, a typical young guy with TT around 650 ng/dL and SHBG of 30 nmol/L has cFT of about 15 ng/dL.

that scale is Quest lab, Labcorp scale is 8.7 - 25.1 pg/ml

perhaps the best interpretation of the Quest result on LabCorp scale would be over the top range?

 

[Gianluca]

Below is a graph from the work referenced by @madman. This give a feel for the kinds of differences you can expect with different injection sites and methods. This is using nandrolone decanoate, and suggests a much longer half-life for subQ. In the Antares study the half-life for subQ T enanthate was about 50% longer than for IM.
View attachment 7106

basically after all, on SubQ we might never get to a higher level of Test, of course unless more Testosterone is used, but the curve looks better than all

 

[Cataceous]

that scale is Quest lab, Labcorp scale is 8.7 - 25.1 pg/ml

perhaps the best interpretation of the Quest result on LabCorp scale would be over the top range?

The LabCorp result is from the inaccurate and unreliable direct free T test. It's a totally different scale and cannot be compared except with where you are in the range, and then only if it happened to be an accurate result.

 

[Cataceous]

basically after all, on SubQ we might never get to a higher level of Test, of course unless more Testosterone is used, but the curve looks better than all

You're getting the same amount of testosterone either way. It would just take longer to stabilize with subQ. If you're injecting frequently compared to the half-life then eventually serum testosterone will end up about the same with either IM or subQ. If you're injecting infrequently then serum levels with IM will go higher and lower than with subQ, but the average levels are the same.

 

[HealthMan]

I think so, I know for sure I need to be over 22 of FT to feel good, and If I try to surpass that number on SubQ I'm not sure how much I should use.

Also last year I was doing 20mg everyday IM, that brought my FT at 30, just switching 2 injections sites per week SubQ lowered my FT at 22, and I thought I felt the difference immediately.

The good thing I have experienced when switching SubQ, is that my face started to look "dryer" and more youthful again, either because my FT lowered or because the much slower absorption of Test, even though I was doing a tiny 20mg daily

If you feel better keep that way. At least for me Subq absorption was really poor (using TT as a proxy for absorption). I didn’t feel as good.

 

[BJE]

what is your HCG protocol? I was doing daily HCG 150IU and If I remember correctly it did not effect my FT levels

I’ve been all over with it but I’m currently injecting 333IU every other day.

 

[Gianluca]

If you feel better keep that way. At least for me Subq absorption was really poor (using TT as a proxy for absorption). I didn’t feel as good.

the only good thing I notice subQ is that my face would look less bloated and more youthful

 

[Gianluca]

I’ve been all over with it but I’m currently injecting 333IU every other day.

I believe that might work for raise a bit of testosterone, small daily dose of HCG won't

 

[Gianluca]

You're getting the same amount of testosterone either way. It would just take longer to stabilize with subQ. If you're injecting frequently compared to the half-life then eventually serum testosterone will end up about the same with either IM or subQ. If you're injecting infrequently then serum levels with IM will go higher and lower than with subQ, but the average levels are the same.

I'm getting the same amount but it possibly never reach a high enough level compare to IM. Looking at the graph, if I'm understanding it well, subQ will produce a really stable curve and never peak, when IM reaches a higher level as much as 3 x, and by the time it will come down it is time for another injection, of course all approximately since that graph represent Deca IM vs SubQ. Hypothetically if with 100mg IM we get a FT of 25, subQ we might need 200mg

Again then it is all subjective

 

[Cataceous]

I'm getting the same amount but it possibly never reach a high enough level compare to IM. Looking at the graph, if I'm understanding it well, subQ will produce a really stable curve and never peak, when IM reaches a higher level as much as 3 x, and by the time it will come down it is time for another injection, of course all approximately since that graph represent Deca IM vs SubQ. Hypothetically if with 100mg IM we get a FT of 25, subQ we might need 200mg
...

This would only be true if you were injecting infrequently and only looking at peak values. But average levels should be about the same for the same doses. The data do not support the idea that some large fraction of subQ-injected testosterone just disappears. Suppose you were injecting 15 mg of T cypionate daily IM and measured your—pretty constant—serum testosterone at 800 ng/dL. If you then switched to subQ and waited long enough then your serum testosterone would still be around 800 ng/dL.

If you're looking for higher testosterone peaks then you can still accomplish this with subQ injections: You switch to a shorter ester. For example, go to enanthate from cypionate, or to propionate from enanthate.

 

[BJE]

This would only be true if you were injecting infrequently and only looking at peak values. But average levels should be about the same for the same doses. The data do not support the idea that some large fraction of subQ-injected testosterone just disappears. Suppose you were injecting 15 mg of T cypionate daily IM and measured your—pretty constant—serum testosterone at 800 ng/dL. If you then switched to subQ and waited long enough then your serum testosterone would still be around 800 ng/dL.

If you're looking for higher testosterone peaks then you can still accomplish this with subQ injections: You switch to a shorter ester. For example, go to enanthate from cypionate, or to propionate from enanthate.

I only inject SQ but I have tried different dosing schedules and when I dose daily I have to greatly reduced my weekly total dosage in order to not be way over top of the chart in all test levels. Dosing twice a week I can dose a much higher weekly total and not go over the top on testing day. However I feel much better at the higher weekly dose and twice weekly injections. This I’m sure is because although I don’t test high on test day, I’m spending a couple of days at a peak well over the top of the chart before it drops back to normal. With daily injections l’m injecting a lower weekly amount
and have a constant lower test level.

 

[Cataceous]

I only inject SQ but I have tried different dosing schedules and when I dose daily I have to greatly reduced my weekly total dosage in order to not be way over top of the chart in all test levels. ...

Yes, this is expected when measuring trough values. More frequent injections flatten out the serum levels so the troughs are higher and closer to the average.

 

[Gianluca]

This would only be true if you were injecting infrequently and only looking at peak values. But average levels should be about the same for the same doses. The data do not support the idea that some large fraction of subQ-injected testosterone just disappears. Suppose you were injecting 15 mg of T cypionate daily IM and measured your—pretty constant—serum testosterone at 800 ng/dL. If you then switched to subQ and waited long enough then your serum testosterone would still be around 800 ng/dL.

If you're looking for higher testosterone peaks then you can still accomplish this with subQ injections: You switch to a shorter ester. For example, go to enanthate from cypionate, or to propionate from enanthate.

that is a good point, I'm waiting to discuss this with Dr Saya, see what he believes

 

[easternpromise]

I wanted to just throw in my experience. I feel like when I switched from SubQ to IM I felt so much better. I saw positive changes in a short time with IM. I feel like I wasted less as well, with SubQ I always got some leakage.

 

[Gianluca]

I wanted to just throw in my experience. I feel like when I switched from SubQ to IM I felt so much better. I saw positive changes in a short time with IM. I feel like I wasted less as well, with SubQ I always got some leakage.

wasted you mean your muscle mass? what was your subQ protocol?

 

[easternpromise]

Wasted the actual testosterone. Lots of leakage for me.

 

[xqfq]

Below is a graph from the work referenced by @madman. This give a feel for the kinds of differences you can expect with different injection sites and methods. This is using nandrolone decanoate, and suggests a much longer half-life for subQ. In the Antares study the half-life for subQ T enanthate was about 50% longer than for IM.
View attachment 7106

How soon after a protocol change do you think it’s acceptable to get blood work done if someone is doing subQ testosterone injections?

I usually use SteroidPlotter - Graph your cycle, but it sounds like this should be adjusted for subQ if it does have a 50% greater half life.

 

[Cataceous]

How soon after a protocol change do you think it’s acceptable to get blood work done if someone is doing subQ testosterone injections?

I usually use SteroidPlotter - Graph your cycle, but it sounds like this should be adjusted for subQ if it does have a 50% greater half life.

The confounding factor in that Xyosted study is that they don't use benzyl alcohol with their subcutaneous enanthate. We think this may account for the exceptionally long measured half-life, ~10 days. For further confusion, it also seems likely that the dose size affects the apparent half-life, with larger doses having larger values.

I would continue to use the SteroidPlotter site. The numbers it uses are pretty decent for a first approximation. They are also often consistent with anecdotal reports—at least those involving enanthate, cypionate or propionate. With these numbers, four weeks after a protocol change should be adequate for testing with cypionate or enanthate. In the case of propionate a week should work for most people.