Opioids Methadone- Drastic Varience in Oral Bioavialability & Toxic Metabolites?

[muie]

First,Wikipedia lists the oral bioavilability of methadone in between 40% to 90%. The difference between 40% bioabilability & 90% is immense! Not to mention that such drastic differences can be extremely dangerous (even to experienced users).

May someone please elaborate on what causes such huge variables in the oral bioavilability of methadone?
For example how may one acheive maximum bioavilability (oral) while on the same note, what may cause one to absorb such little methadone (with only 40%-50% bioavilability)?

Second, it has been said by medical proffesionals that the use of methadone in pain management is superior to that of other opiods, due to the fact that (begin quote):

"Opiates, such as morphine, produce metabolites when they are broken down within the body. These metabolites can build up in the body and cause symptoms of opiate toxicity. Opiate toxicity is essentially an overdose of an opiate leading to poisonous levels in the body and causes symptoms such as restlessness, hallucinations, tremors and lethargy.

Methadone doesn’t produce metabolites and therefore doesn’t have a “ceiling," or maximum dose. Methadone is also easier to metabolize by the liver, and its lack of metabolites makes it an excellent choice of pain medication for many patients with decreased liver function or renal failure."- (end quote).

I don't know how much truth there is to this claim as methadone's two main metabolites are EDDP and EMDP. I am not sure if I understand the concept of opiate toxicity correctly, since I assume the metabolite/s have to be active in order to be considered toxic?!

1. Can someone please shed some light on methadone's metabolites and confirm the quote I posted?

2. Will someone please explain the concept of opioid toxicity and how it relates to metabolites?

Many thanks!

 

[sekio]

The variation in bioavailiability is mostly determined by individual genetics and physiology, stomach pH, and presence or absence of food.

Methadone does produce metabolites; I'm not sure they're active as opiates in the same way the metabolites of morphine are (the glucuronides of morphine at least). I think that (badly-phrased) quote was referring to *active* metabolites building up and resulting in symptoms similar to an opiate overdose.

Whether or not an opiate drug produces metabolites should have no effect on the "ceiling" dose. It's only in the case of prodrugs like codeine that this is something to consider.

Opiate toxicity is usually the result of an overdose or some secondary action of the drug (methadone fucks with potassium channels I think).

 

[bnghit3]

Isn't it also true that no matter the ROA methadone has the same bioavialability. I have heard that it doesn't matter if you snort shoot or eat the methadone its going to be the same. Is this true, i use methadone all the time, but always just take it oral.

 

[Captain.Heroin]

Methadone in itself can be toxic; I wouldn't believe what wikipedia said here primarily because methadone is not superior to other opioid analgesics.

The primary difference with methadone is that it is also an NMDA receptor antagonist. I think this difference will make it a more attractive option for pain relief for people who don't find that other full agonist opiates work well for them.