RogueRose - 27-4-2018 at 19:45
So I've always wondered how some drugs are made to be longer acting and this can be done in many ways but one of them is adding an ester to the
compound which, if I'm not mistaken, slows the metabolic breakdown of the active compound allowing for a longer half life by slower metabolic
breakdown.
One compound which everyone has is testosterone and this is one compound that is made with many different esters making them active from hours to many
weeks and even a month half life. I found that there is even one ester that allows for the compound to be orally ingestible and active where the
others are not, and this is the most confusing function of the ester and how it could make it active orally. This ester is very long and heavy.
For example
Testosterone base is 288g/mol - 2-4hr half life - no oral activity
Test propionate 344.5g/mol - 14-18 hr half life - no oral activity
Test enanthate 400g/mole - 4-5 day half life basically inactive orally
Test undecanoate 456g/mol ~30 day half life and ~4-7% orally available
What I'm not certain of is what these esters are, if they are unique to the testosterone molecule or if they can be added to other compounds to give
similar effects in making the drug last longer.
I also know that testosterone base is a white dry powder but as soon as an ester is added it becomes what looks to be a waxy substance and I've been
told that it melts very easily like wax, and the "heavier" the ester, the more it moves through the waxy stage to the point of almost being an oil at
room temp.
I remeber reading some time ago when researching plant oils IIRC, there were acid names that corresponded or were related with the above esters. I
think they were carboxylic acids
https://en.wikipedia.org/wiki/Carboxylic_acid
What is interesting is that Acetic acid is a carboxylic acid and is the only one with 2 carbon atoms with the formula CH3COOH. From there there are
17 more acids, with each adding a methylene group (CH2), and each being a new acid, so the next acid in line would be CH3CH2COOH, then CH3(CH2)2COOH,
CH3(CH2)3COOH - noticing that the (CH2)x being the difference in each acid. I'm sure this isn't new to most of you on the site, but it took me a lot
of reading years ago to come across this and put things together and I didn't understand it well when I did.
So what I'm wondering is if the above esters of testosterone are made by simple adding the corresponding carboxylic acid to the base compound? Much
like taking a drug and adding HCl or H2SO4 to make the hydrochloride or sulfate version of the drug?
If my theory on how this works is correct, using the carboxylic acids on the base, then that makes sense why it takes longer for the body to
metabolize it as it breaks down the CH2 during each pass through the system.
Anyone have experience in this? The odd thing is is that I've asked a number of doctors and pharmacists and they had absolutely no idea, not even the
slightest notion of what I was talking about (I think they thought I was delusional or making things up...)
Texium - 27-4-2018 at 20:44
The body definitely does NOT break each methylene off of the ester group as you suggest. While that is an interesting bit of speculation on your part,
it simply does not hold up with reality. Adding the ester improves the bioavailability and the half life because adding the hydrophobic chain to the
molecule, such as with the undecanoate, which adds an 11 carbon straight-chain hydrocarbon to the molecule, makes the molecule more fat-soluble, and
therefore more readily taken up from the digestive system when taken orally, and less likely to be excreted. It is actually quite the opposite of
taking a drug as a hydrochloride salt or similar- those are produced as salts to improve water solubility. Depending on the drug, it either needs to
be water soluble or fat soluble to be effective. It just depends on what the purpose of it is, and where it needs to be delivered.