Pharmacokinetic Profile of Testosterone Suspension: A Case Study

[Cataceous]

Lately I’ve been insinuating that some testosterone suspension products may qualify as fast-acting, and therefore be in the same league as testosterone nasal gels and buccal troches. The “fast-acting” quality is important if the goal is to retain HPTA function in the presence of exogenous testosterone. It was time to put my money where my mouth is in order to see what’s actually happening when I inject testosterone suspension.

The results are promising, but not as definitive as I’d hoped for due to some confounding factors.

Materials and Methods

The product used was Pharmacom testosterone suspension (TS), 100 mg/mL, diluted with bacteriostatic water to a nominal 50 mg/mL. It was believed that existing HPTA activity could result in a nontrivial baseline of endogenous testosterone. In an attempt to reduce that, two 250 mcg doses of ganirelix were procured and injected subcutaneously at 10 hours and 3 hours prior to the subcutaneous injection of a dose of 3 mg—6 units—of the TS. Ganirelix is a GnRH antagonist more commonly used in women. Ganirelix seemed appropriate here because its 13 hour elimination half-life would not lead to prolonged HPTA suppression.

Baseline serum total testosterone was measured by Labcorp ECLIA just prior to the TS injection, along with albumin and SHBG. Serum total testosterone was subsequently measured at 0.5, 1, 2 and 4 hours post-injection.

Results

Baseline SHBG was 40.5 nMol/L. Albumin was 4.1 g/dL. Baseline serum testosterone was 270 ng/dL (!). Changes from baseline testosterone are as follows:

Discussion

The fast post-injection rise in serum testosterone and Tmax of 30 minutes are promising with respect to the premise of fast action, as is the relatively large drop from the one-hour level to the two-hour level. The latter yields a half-life of about 1.7 hours, in line with the manufacturer’s claim of two hours. However, the four-hour blood level is confounding, suggesting a much longer half-life if taken verbatim.

The relatively high baseline testosterone of 270 ng/dL was unexpected. The hope had been to drive it below 50 ng/dL. The reason for the high level is unclear. Two possibilities: the ganirelix was ineffective for some reason; or there was a nontrivial residual from the previous injection of a nominal 1.5 mg TS, which took place about 16 hours prior to the study injection. Either case is problematic with respect to the TS half-life. If the ganirelix was ineffective then endogenous production during the study could interfere with determining the half-life. If there was a significant carryover from the previous injection then the implication is a much longer half-life than expected. There could be a combination of the two factors, or something else entirely.

The area under the curve is troublingly small, possibly 20-fold lower than expected. This is difficult to explain, and the magnitude of the discrepancy makes the obvious explanations seem very unlikely. These include under-dosing of the product, improper dilution, and injection-site leakage. Another explanation with marginal plausibility is that the 31 gauge needle acts as a filter, excluding larger particles and greatly reducing the effective concentration.

Acknowledgements

Thanks to Defy Medical for their willingness to prescribe ganirelix. Thanks to the staff at my local Labcorp location for their cooperation and assistance.

 

[FunkOdyssey]

I love that you did this experiment and wrote up all of the details for us. Very puzzling results though!

 

[Willyt]

Thanks Cat for the attempt to isolate the effects of Suspension. What are your next steps?

Would be interesting to see the TT/FT/HPTA blood results when available

I continue to dabble with TNE oil-base which subjectively speaking seems to stick around longer than water-based Suspension

 

[Cataceous]

... What are your next steps?
...

I've taken the first one, which is to investigate where the missing testosterone went. It appears likely that the filtering action of a small needle is part of the problem, along with wastage via particle deposition on the vials. The empty vial that had contained 1 mL of the TS and 1 mL of bacteriostatic water had noticeable residue after all of the fluid was eventually removed and injected. I dissolved this residue in 2 mL of ethanol and heated it in an open container to 120° C (~250° F) for about 20 minutes. I did the same with a control sample of 2 mL ethanol, to account for impurities in the alcohol. With the ethanol evaporated the weight of the control residue was at most 10 mg. The weight of the TS residue was 160 mg (!). The fact that the weight of this residue is more than the nominal initial testosterone content of 100 mg is a new puzzle. Typical TS excipients (sodium phosphate dibasic, polysorbate 80, sodium chloride) are highly water soluble and thus should not remain in significant quantity when the bulk of the liquid has been removed. In any case, this result suggests that a lot of the testosterone was not withdrawn by the 31 gauge needle. I also noted a lot of residue in the stock TS 10 mL vial, even after evacuation with a large bore needle. Using the same technique as above I found this residue to weigh 220 mg. It seems suspect that a single 1 mL withdrawal and the stock vial residue would together contain more than a third of the nominal total testosterone in the vial. But I don't have another explanation unless there is some other excipient that is precipitating in situ.

If this explanation for the lack of testosterone is correct then it could have an effect on the measured pharmacokinetics. If only the smallest 5-10% of particles are being used then we might expect this to result in faster absorption and a smaller apparent half-life. It's also a remarkably inefficient way to use TS. In hindsight it would have been more useful to the TRT community if I had used a larger-bore needle along with the stock TS product. I'm not ready to do this now, as I'm heading in a slightly different direction. Perhaps a Defy patient would volunteer, as then it's a relatively inexpensive experiment—$100 for the five testosterone tests.

Where I'm headed with this is to try adding different solvents to the TS with the hope of attaining smaller particles overall via some dissolving, which in turn should allow continued use of 31 gauge needles and the desired fast action, along with less waste. I'm starting a trial in which the 1 mL of bacteriostatic water is replaced with 0.8 mL of polyethylene glycol 400 and 0.2 mL of benzyl alcohol. Visually the result is better, with the individual testosterone particles appearing less prominent and less prone to deposition on the vial sides. However, only time will tell if this is a useful formula.

A further drawback of the ostensible micro-dosing with TS is that it calls into question claims about HPTA function. That is, if I'm only taking on the order of 1 mg per day of testosterone then I can't tell whether HPTA activation is due to the fast-acting nature of the testosterone or to the low dose itself. On the other hand, it's a remarkable finding that dropping to such a low dose of testosterone can lead to consistently good results in potential problem areas: libido↑, sexual function↑; even non-problem areas: lipids↑; at the expense of athleticism↓, maybe body composition↓→.

 

[Guided_by_Voices]

it's a remarkable finding that dropping to such a low dose of testosterone can lead to consistently good results in potential problem areas: libido↑, sexual function↑; even non-problem areas: lipids↑; at the expense of athleticism↓, maybe body composition↓→.

FWIW, I've found the same thing when I cut my dose of Test cyp, at least in the short term. I would do so permanently and add in Oxandrolone for the anabolic effects, except that my E2 is already very low and I haven't wanted to get into supplementing E2 directly.

 

[Forty2]

FWIW, I've found the same thing when I cut my dose of Test cyp, at least in the short term. I would do so permanently and add in Oxandrolone for the anabolic effects, except that my E2 is already very low and I haven't wanted to get into supplementing E2 directly.

Have you tried hCG with low dose Oxandrolone on hard workout days?