I wrote a little about the pharmacokinetics of AAS in a couple of replies to a thread back in March:
https://www.eroids.com/forum/steroids-qa/anabolic-steroids/esters-where-...
I thought I’d make it part of a short essay I hope some of you will enjoy. If you have any questions I’ll try to give you some answers.

I remember this from undergraduate lectures: pharmacokinetics – what your body does to the drug, pharmacodynamics – what the drug does to your body. What AAS do to your body is generally of more interest to users but interesting examples of both are seen in the differences between the structurally similar AAS dianabol and boldenone. The free base steroid molecules are identical apart from the methyl group attached to C-17 of dianabol where boldenone retains a hydrogen atom at this position in common with testosterone. This imparts distinct pharmacokinetic differences.

C-17 methylation interferes with the ability of two classes of liver enzymes, sulfatases and uridine glucuronyl transferases, to conjugate dianabol with a sulfate or glucuronide moiety on the hydroxyl (OH) group also attached to C-17. This interference is simply by virtue of its close proximity. The methyl group physically gets in the way of the enzyme on the molecular level and this is known as steric hindrance. Conjugation renders a steroid inactive, more polar (water soluble) and likely to be excreted in bile or urine. This particular hindrance to metabolism is a pharmacokinetic property not possessed by boldenone. Free base boldenone is readily metabolised in the liver by conjugation. Thus dianabol can be taken orally but boldenone cannot. Boldenone’s action in the body is prolonged by esterification of the hydroxyl group on C-17 through reaction with a carboxylic acid, typically as the undecylenate but also seen as the cypionate and acetate esters.

What about the pharmacodynamics effect of the C-17 methylation of dianabol compared with boldenone? Methylation makes dianabol a more potent androgen than boldenone. Just think about the typical doses of each. Interestingly this effect also extends to their oestrogenic metabolites. Aromatisation rates of both dianabol and boldenone are unsurprisingly similar since this reaction is well removed from the only difference between the two on C-17. Boldenone has limited oestrogenic side effects whereas dianabol is well known for causing water retention and a red face. Without an AI 50mg/day of dianabol quickly results in bloating and high blood pressure. 350mg/week of boldenone without any other aromatising steroids would not normally require any attention to oestrogen control at all. Why? There are similar amounts of oestrogenic metabolites but C-17 methylation makes for a more potent oestrogen.

So what happens when a C-17 methylated AAS is ingested orally? It is absorbed into blood from the small intestine and transported to the liver via the hepatic portal vein in a process known as first pass metabolism. In this way all of the ingested AAS is exposed to hepatic metabolism before being allowed to enter systemic circulation and subsequent distribution to target tissues like skeletal muscle. A significant proportion of C-17 methylated dianabol passes through the liver unmetabolised and remains active. This fraction is described as bioavailable. Boldenone has no methyl group interfering with access to the hydroxyl group on C-17 and is readily metabolised by conjugation. Its oral bioavailability is close to zero.

But what if a steroid is esterified? There have been some attempts to increase the oral bioavailability of AAS with long esters, such as with testosterone undecanoate. This ester is significantly fat soluble and may be absorbed from the small intestine and into lymphatic circulation. Lymph fluid drains into blood circulation via the thoracic duct near the heart, permitting the ester to enter systemic circulation without encountering first pass hepatic metabolism. This sounds like a promising alternative to the hepatotoxicity produced by C-17 methylation but unfortunately the reality is a poor second. Consider the doses of testosterone undecanoate administered to produce therapeutic concentrations of testosterone; an average of 100mg/week or less as an intramuscular injection (Reandron) compared with oral doses that may be more than 100mg/day (Andriol).

Esterification delays the release of AAS as active free bases so that dosing may be daily, EOD, weekly or somewhere in between, depending on the half-life of the ester. In a simplistic way shorter esters are more readily hydrolysed by enzymes called esterases and so have shorter half-lives. Acetate and propionate esters have a half-life of approximately a day while decanoate and undecanoate esters have half-lives of one to two weeks or more.

Every tissue in the body has esterases. It is to protect the body from acetylcholine that leaks from the neuromuscular junction. When a nerve impulse communicates the signal to contract to a motor unit in skeletal muscle it is by way of the neurotransmitter acetylcholine, or choline acetate. Insecticides and nerve gas typically act by blocking the activity of esterases. Acetylcholine activity then persists and causes uncontrolled muscle spasms. Picture the fly that has been sprayed with insecticide. It buzzes and twitches uncontrollably until there is no more energy reserve left to drive muscular contraction and it subsequently dies from a flaccid paralysis.

The following is the part extracted and edited from a thread I posted in back in July and included here…

AAS, esterified and un-esterified, are both practically insoluble in water. Likewise in blood. When they diffuse out of muscle and into blood they travel bound tightly to proteins in blood and not in solution. Esterases will act on AAS in muscle tissue and in blood. AAS will unbind from the proteins to which they are bound and diffuse into tissue from blood. While they’re bound to the soluble proteins in blood they can pass through the liver without entering the liver cells where they would be metabolised. Some do unbind from the protein and diffuse into liver cells. The same goes for the kidneys. While bound the AAS is not filtered out of blood and into urine. If unbound and free in the water component of blood as it passes through the kidneys it can be filtered into urine and excreted.

AAS that have been conjugated with a water soluble moiety are much more water soluble and will likely stay dissolved in the water component of blood, not bound to a protein. They can then be freely filtered by the kidneys and excreted. Often AAS metabolites are excreted into bile by liver cells. The bile travels into your small intestine and you subsequently excrete the steroid by shitting it out. Isn't science fascinating?

The concept to grasp is that the whole process is dynamic and composed of nearly countless numbers of molecules. Some stay bound, some diffuse from proteins into liver or muscle or other tissue. Some is still present as an oily depot in your glute.

When you get a blood done for test levels you normally get a total test level and a free test level. The free test level is always lower than the total test level. It represents the proportion of the total test in your blood that is not bound to proteins and is free to diffuse into other tissues (like muscle, liver or kidney) or interact with things like enzymes (eg esterases) or receptors (eg androgen receptors). Sex Hormone Binding Globulin (SHBG) is a protein synthesised by your liver specifically for binding sex hormones (eg test and oestrogen) in blood. It also binds AAS. It is often in your blood results too. Androgens reduce its synthesis and oestrogens increase its synthesis. When you take test your total test goes up but your free test goes up proportionately more because your SHBG goes down. When your test goes down during PCT you need to watch your oestrogen because it can make your SHBG go up and push your free test even lower.

Oh, and if you think I just copied and pasted this from Google then go fuck yourself. ;-)

Cheers

Dr B