A question about metabolites

[QUARE]

I was reading about Bupropion and I saw those metabolites and I was wondering how all this works.

Bupropion have a half-life of 10h so from my understanding it takes about 20h for the effects of Bupropion alone to be completely gone. Is this wrong ?

Than theres those metabolite;
- R,R-Hydroxybupropion have a half-life of 21h
- S,S-Hydroxybupropion have a half-life of 25h
- Threo-hydrobupropion have a half-life of 26h
- Erythro-hydrobupropion have a half-life of 26h

My question is when do these metabolite appear in our blood stream ?

Do they appear all togheter from Bupropion and after how much time ? or do they appear one after each other ?

How long does it takes to metabolise all these chemicals and have nothing left from Bupropion and its metabolites ?

How does this work in general ?

 

[Psychedelic Jay]

The effect of the drug last as long as active levels are in the blood of it and active metabolites.

 

[tweex]

My question is when do these metabolite appear in our blood stream ?

The direct metabolites are going to start appearing almost immediately after the medication gets into your bloodstream.

Do they appear all togheter from Bupropion and after how much time ? or do they appear one after each other ?

I'm not sure which ones are direct, which ones are indirect, and which ones appear in higher concentrations than others. The direct metabolites are all going to start showing up at the same time, although maybe at different rates with the more major ones in higher concentrations, obviously. Then any indirect (or secondary) metabolites are going to start showing up in far lower concentrations proportional to the concentration of the primary metabolite, again almost immediately, and any metabolites of metabolites of metabolites at even lower concentrations proportional to the secondary metabolite, etc...

How long does it takes to metabolise all these chemicals and have nothing left from Bupropion and its metabolites ?

Theoretically, never. Half-lives are just that, half-lives. In practice you are going to stop noticing any effects after 1-2 half lifes of the last active metabolite, and it will stop being detectable in tissue some many half-lives after that.

How does this work in general ?

http://en.wikipedia.org/wiki/Chemical_kinetics

 

[sekio]

Bupropion have a half-life of 10h so from my understanding it takes about 20h for the effects of Bupropion alone to be completely gone. Is this wrong ?

That is incorrect. Most drugs decay with an exponential curve (first-order metabolism), not a linear one. (Except for some drugs, like alcohol, which are metabolised at a constant rate (zero-order)). And half-life measures the concentration of the drug only - not the effects produced by the drug.

What this means is: Say a drug has a half life of 10 minutes. and say at T=0 minutes, 100% of the drug is present.
After 10 minutes, 50% of the drug remains.
After 20 minutes, 25% remains
After 30 minutes, 12.5% remains.
After 60 minutes (1 hour), 1.56%.
After 120 minutes (2 hours), 0.024%.

What happens to the other 99% of the drug? It is either metabolised to some other compound, or it is excreted somehow. If the drug has active metabolites you should be careful because the half-life of the parent compound may not neccesarily predict the total duration of effects. (For instance, the half life of heroin in vivo is shorter than you would expect given its duration of effects, because it is a prodrug for morphine)

My question is when do these metabolite appear in our blood stream ?

Generally they start appearing as soon as the drug reaches cells equipped to break it down (e.g. the liver, or blood, or whatever). So, metabolites appear almost immediately after the drug enters the circulation. You would have to look at a study or two to determine how much of each metabolite is generated and when they reach peak concentrations.

How long does it takes to metabolise all these chemicals and have nothing left from Bupropion and its metabolites ?

The rule of thumb is that most drugs need around 7 half-lives to clear out to less than 1% of their initial concentration. It's rare that you completely eliminate every last trace of the drug. But in practice, the levels will fall below the minimum detection limit eventually.