Hi, after reading numerous posts I am intrigued to find out the mechanism of an intramuscular injection. I wonder if other members could help? The doses that members need are considerably more than the NHS prescribe. I know that some vitamins in high doses can have pharmaceutical effects. Vitamin K is a antidote for Warfarin, Bodybuilders use B3 to pump their muscles up and increase vascularity, high dose Vitamin C is widely touted for improving a variety of conditions.
Once the B12 has been injected in the muscle I assume that the blood vessels will gradually clear it and during the process it will circulate and be taken up by the body's cells. I read that some IM drugs are oil based so maybe these last longer in the muscle and are removed slower? The B12 is in a saline solution so might be taken quicker. Will the level in the blood decrease in strength as the depot is used up in the half-life principle like oral drugs? eg the level of the drug will be half in say 12 hours, then half of that again in another 12?
Once the body's cells have enough how long before they need to be topped up and if the liver takes B12 up might that not again become the repository for future B12 to the body till its exhausted? I cannot find any research on the subject and might it shine a light on future treatment?
Regards John
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john159
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The pharmacodynamics of B12 are not at all simple.
The B12 gets deposited in the muscle (or fat, many people do subcutaneous injections). From there it slowly diffuses in the liquid between the cells until it encounters a blood vessel and enters the blood. This process happens relatively slowly so that most of it has got into the blood after a few hours. Nobody knows it it happens faster from an IM injection or a SC injection.
Once in the blood it will bind to one of two proteins, Haptocorrin (HC) or transcobalamin (TC). Only the TC-B12 can enter the cells. It is called 'active' B12 or holotranscobalamin. Nobody is quite sure of the purpose of HC-B12.
Stuff that doesn't bind to one of the these proteins will get filtered out in the kidney. Some of this is reabsorbed. But that reabsorption has a fixed capacity. So, if there's a lot of free B12 in the blood, then much of it will not be reabsorbed and will pass out in the urine.
Much of the B12 in the blood (I'm not sure, but I think it's mainly HC-B12) will be stored in the liver. From there, some will be passed out into the duodenum (the first part of the small intestine) in the bile. Once in the duodenum the HC-B12 bond will be broken and the B12 will be free to attach to any Intrinsic Factor that is present (having been made by Gastric Parietal Cells in the stomach). The IF-B12 will travel down to the ileum where it will be absorbed and the B12 passed back into the bloodstream. It's called enterohepatic recirculation.
However, if you have PA then you don't have any GPCs and, therefore, no IF. So the B12 secreted in the bile passes straight through the gut and down the toilet. People say your liver stores 4 years of B12, but much (all?) of it in inaccessible. I don't think all of it is inaccessible (otherwise PA wouldn't take years to show itself) so there must be some other way for the B12 in the liver to get back into the blood in a usabel (TC-B12) format.
Because of all this complexity you cannot give a value for the half life of B12. Not one that would allow you to do useful calculations. There are just too many variables and too many unknowns.
This is my guess at what blood concentration of B12 will look like after a single IM dose.]
Thank you fbirder for a very informative reply. Since most of the B12 ends up being excreted by the kidneys I wonder if patients on multiple frequent doses would be better with a small regular dose? The loading regimen with 6 injections over a short period loading up the Liver or somewhere else in the body? Maybe the reason PA takes 4 years to show is that the parietal cell numbers decline slowly as they are destroyed by the immune system so the Active B12 reduces over time?
Yes, smaller, more regular, doses would be preferable. Several people are investigating the possibility of slow-release B12. So you could inject 1000 mcg and it would slowly move from the injection site into the blood over several weeks. That would work much better than the current regimen.
The loading doses are done to get the whole body replete - blood, liver and all the other tissues where B12 is found.
That's a very good point about the slow destruction of GPCs. I hadn't thought of that. Thanks.
If this indeed happens then perhaps the body resists the destruction of the cells in some way. The body usually does all it can to keep everything the same. If it can resist then can it reverse? I have come across people with type two bipolar disorder that is periods of depression followed by periods of high activity levels ( not hyperactivity or mania). My long lasting bipolar type two was gone within weeks of EOD and 16 months on has not returned. If research shows this to be true then it might open up the possibility of cure. Unfortunately doesn't feel we are anywhere close to that yet.
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