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Amphetamine and CYP450 metabolism

Lightning-Nl

Lightning-Nl

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Nov 11, 2012
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Quick question here today.

Amphetamine pharmacokinetic metabolism is also cytochrome p450 mediated (CYP2D6). Putting aside the fact that grapefruit juice (for instance) is acidic, If you were to take a CYP450 inhibitor with amphetamine, it stands to reason that would cause more amphetamine to build up in more concentrated amount in plasma, correct?

I know that's would definitely work...in theory. Just wondering if there's something I'm missing that would cause this to not be the case. Thanks guys!
 
On paper, yes, some small amount. But I don't think metabolic breakdown of amphetamine via CYP enzymes is very significant. I seem to recall most of it is metabolised by MAO to phenylacetone.
 
sekio said:
On paper, yes, some small amount. But I don't think metabolic breakdown of amphetamine via CYP enzymes is very significant. I seem to recall most of it is metabolised by MAO to phenylacetone.
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So a Monoamine Oxidase Inhibitor would be way more practical is what your saying, right?

I know they always tell you not to take an MAOI but is it really that dangerous? I'm assuming you wouldn't want to take something as powerful as a prescription MAOI with amphetamine. But in minuscule doses, would that be dangerous?
 
.... No, don't take a MAOI with amphetamine. That's asking for a hypertensive crisis. In fact, why are you even trying to block the metabolism of amphetamine? More than 30% of an ingested dose of amphetamine isn't even broken down and is excreted unchanged. Is an extended release formulation of amphetamine not suitable?
 
sekio said:
.... No, don't take a MAOI with amphetamine. That's asking for a hypertensive crisis. In fact, why are you even trying to block the metabolism of amphetamine? More than 30% of an ingested dose of amphetamine isn't even broken down and is excreted unchanged. Is an extended release formulation of amphetamine not suitable?
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This is actually more an "in theory" kind of question.

I purposely made it sound like I was actually going to try it in order to get your natural reaction to the question.
 
SwampFox56 said:
This is actually more an "in theory" kind of question.

I purposely made it sound like I was actually going to try it in order to get your natural reaction to the question.
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A lot of the grapefruit juice concentrations lead to significant drug interactions only with chronic use. I doubt having half a grapefruit and then taking your amphetamine will significantly affect its pharmacokinetics.

IMO the best way to get more effects from a drug/medicine is to adjust the dose or formulation. Purposefully messing with CYP enzymes or manipulating pH levels is usually an inexact science, or you may well end up overdoing it for that matter.
 
Fucking around with stomach pH will generally only change the amount of amphetamine absorbed, & the rate it's absorbed at. Eating tums won't change urinary or blood pH so won't change the lifetime of amph in the blood.
 
sekio said:
Fucking around with stomach pH will generally only change the amount of amphetamine absorbed, & the rate it's absorbed at. Eating tums won't change urinary or blood pH so won't change the lifetime of amph in the blood.
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Hate to be nit-picky, but if tums allow for more amphetamine to be absorbed, wouldn't that in-turn, result in higher plasma levels of amphetamine? ;)
 
sekio said:
Fucking around with stomach pH will generally only change the amount of amphetamine absorbed, & the rate it's absorbed at. Eating tums won't change urinary or blood pH so won't change the lifetime of amph in the blood.
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It is notably stronger. Tums + a CHO/Pro/Fat meal = Like adderall XR 2.0
 
That's because you absorb something like ~1,5x the amount of amphetamine by adjusting stomach pH, so you'll get another half life or so of effects worth, because you've almost doubled the amount of drug ingested.

Conversely, if your gastric pH stays low the entire time then some amphetamine is not even absorbed.

In the case of adding food to the equation, it just slows absorption because it has to diffuse out of the food.'

In neither of these cases are you actually making amphetamine's half life any longer or shorter, really - you are just fucking around with the ROA, basically.
 
tina&gina said:
Just take a Norvir. It boosts amphetamine levels in the blood.
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That's an awful idea.

Why would you take a drug that could quit possibly make you very ill just to get a little "boost" out of your amps?!

The cons greatly outway the pros in this situation!!!
 
sekio said:
That's because you absorb something like ~1,5x the amount of amphetamine by adjusting stomach pH, so you'll get another half life or so of effects worth, because you've almost doubled the amount of drug ingested.

Conversely, if your gastric pH stays low the entire time then some amphetamine is not even absorbed.

In the case of adding food to the equation, it just slows absorption because it has to diffuse out of the food.'

In neither of these cases are you actually making amphetamine's half life any longer or shorter, really - you are just fucking around with the ROA, basically.
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Yeah but the financial practicality is worth it. Why take 20 XR when you do what I mentioned and get the same level of productivity with 10 mg IR & maybe a coffee or two.
 
Many SSRI's inhibit CYP2D6 and there are certain ones I cannot take with my Adderall without eventually becoming extremely agitated. Prozac and Paxil were the worst. I could really feel the amphetamines building up - it was NOT pleasant. I knew nothing of liver enzyme inhibition at the time.
 
DexyDevil said:
Many SSRI's inhibit CYP2D6 and there are certain ones I cannot take with my Adderall without eventually becoming extremely agitated. Prozac and Paxil were the worst. I could really feel the amphetamines building up - it was NOT pleasant. I knew nothing of liver enzyme inhibition at the time.
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Like Sekio said, CYP metabolism is a secondary mechanism in the metabolism of Amphetamine. I have also been on Paroxetine while taking Adderall, and I actually thought it decreased the effects of Adderall.

Paroxetine and Fluexotine are both pretty weak inhibitors of CYP anyways. More than likely, the effects you felt were either caused by something else or purely placebo.
 
SwampFox56 said:
Like Sekio said, CYP metabolism is a secondary mechanism in the metabolism of Amphetamine. I have also been on Paroxetine while taking Adderall, and I actually thought it decreased the effects of Adderall.

Paroxetine and Fluexotine are both pretty weak inhibitors of CYP anyways. More than likely, the effects you felt were either caused by something else or purely placebo.
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Oh, Paxil totally weakened all the positive effects of the Adderall, but the negative effects which I had not been experiencing before starting to gradually become very, very intense. Perhaps that is simply caused by some other action of the Paxil and Prozac which is unrelated to CYP2D6. Anyway, I now take Pristiq.
 
my dexedrine dose has been the same for 15 years but even the half life and elimination is faster and I am really hyper and obnoxious at 15. I got an enzyme test that tests that among a few to have on file in case the DEA gets weird. I get tired, mature and calm from them and everything else is too weak for me and I can't eat between doses... There was a PRN pharmacist at the place I go and she was livid and thought I was a druggie... the other one that knew me said to seek out testing in case. We found genome testing but I had to pay 1,167 dollars for it. I have tried other things but except for adderall, the rest were sugar pills.
 
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