Does Omaprazole Inhibit CYP2D6 enough to increase Amphetamine bioavailability?

[Soap MacTavish]

The brand name of Omaprazole is Prilosec. I use this stuff almost daily to control some bad heartburn I have. If I understand correctly it reduces acidity levels in the stomach and intestinal tract by reducing acid production and it also inhibits the enzyme CYP2D6.

According to what I have read, acidity in the gut makes amphetamine excrete from the body faster. While a more alkaline gut will allow more of the amphetamine to hang around in the body and for a longer period of time.

Also according to what I've read, anything that inhibits the CYP2D6 enzyme will also increase the level of amphetamine being absorbed by the body.

I have not found a lot of data or experiences regarding this combination. Can someone attest to this indeed being true and any experience you have with this would be greatly appreciated.

When I take my adderall prescription as prescribed (which is usually 3 weeks out of every month) I find that there are significant valleys in between doses and if I could use this technique to extend the length of duration of the amp/d-amp salt combo that would be very helpful to me and would hopefully prevent me from abusing it any more than I already do.

Warm Regards,

Soap

 

[fastandbulbous]

2D6 does O-demethylation doesn't it? Can't see how that would alter amphetamine levels

 

[Soap MacTavish]

I got this from Wikipedia page:
"Taking a CYP2D6 inhibiting drug along with amphetamine will lead to an elevated level of amphetamine in the system and the drug will also remain longer in the body"

There are other mentions of this in that article as well. Some states that acidity in the gut breaks down the pill too quickly for it to be absorbed and hence it is excreted too quickly. This is probably built in to the pill, meaning that the manufacturers intend for around 30% of it to be excreted as amphetamine, they did not design the pill to be absorbed closer to 90 or 100%(which looks like it is possible if I am understanding this correctly)

I know there are other ways to absorb closer to 100% of the amp but those are too rapid of onset and exit. I want to find a way to help my body hold on to the substance for a longer duration. (5 or 6 hours instead of 4)

 

[fryingsquirrel]

Prilosec isn't you're ordinary antacid, but I'll quote from the drug intraction section of a nursing handbook I have laying around. "Antacids- Increases renal (kidney) recycalling, moniter for increased amphetamine affects".

 

[fastandbulbous]

Now that's a much more plausable scenario

 

[Soap MacTavish]

Yeah tried this out twice now and had the same result:

On empty stomach I took 2 20mg Prilosec (Omaprazole) tablets an hour prior to ingesting adderall. Swallowed the adderall tabs and what happened was a significantly delayed and prolonged amphetamine action. My normal duration is 4 hours but this extended it to around 5.5 hours. It was strange because when I first took the tabs i was expecting the usual quick onset of action but this way delayed by 30 minutes, probably by the inhibited enzyme CYP2D6 and alkaline stomach. It also took longer to reach peak plasma by about an hour.

 

[fastandbulbous]

probably by the inhibited enzyme CYP2D6

As far as I'm aware, cyp2d6 plays no role in amphertamine's metabolism as it acts as an O-demethylator (it turns codeine into morphine) and amphetamine doesn't contain any oxygen atoms

 

[MurphyClox]

As far as I'm aware, cyp2d6 plays no role in amphertamine's metabolism as it acts as an O-demethylator (it turns codeine into morphine) and amphetamine doesn't contain any oxygen atoms

...which is only one part of the whole story.
Looking e.g. at Wiki (well, not the most reliable source, but anyway...), among the substrates of CYP2D6 are listed substances like risperidone, amytryptiline, imipramine, debrisoquine and lidocaine. None of those contains an O-alkyl-residue. Ergo: CYP2D6 does more than just O-dealkylation.


- Murphy


P.S. This could help:

Ramamoorthy, Yamini; Tyndale, Rachel F.; Sellers, Edward M.
"Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates"
Pharmacogenetics 2001, 11(6), p.477

Abstract

CYP2D6 is involved in the metabolism of several classes of drugs, including tricyclic antidepressants, selective serotonin reuptake inhibitors and various amphetamines. CYP2D6*10 is an allelic variant, producing an enzyme with Pro34Ser and Ser486Thr amino acid substitutions. Approximately 75% of Asians possess the *10 allele. We sought to further characterize CYP2D6.10 catalytically in vitro in a baculovirus expression system using various substrates and inhibitors, in comparison to CYP2D6.1 (wild-type). Using dextromethorphan (DEX), P-methoxyamphetamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and (±)3,4-methylenedioxymethamphetamine (MDMA), the ratios of intrinsic clearance (Vmax/Km) of *1 to *10 were 50, 34, 22 and 123, respectively. The CYP2D6 substrates amitriptyline, and (+) and (-) methamphetamine (MAMP) are both p-hydroxylated and N-demethylated (NDM). The intrinsic clearance *1/ *10 ratios were 42, 30 and 67 for the p-hydroxylation; and 60, 120 and 157 for the NDM, respectively, illustrating chemical pathway and enantiomeric selectivity for MAMP. It was apparent that (+) and (-) MAMP NDM and MDMA demethylenation were most significantly different in CYP2D6.10. Using DEX as the substrate, the ratios of Ki (*10)/ Ki (*1) for inhibitors were: budipine (1.3), sparteine (1.6), debrisoquine (8.1), fluoxetine (16), norfluoxetine (30), paroxetine (14), MDMA (21) and MMDA-2 (7.1), indicating that CYP2D6.10 shows drug-specific altered susceptibility to inhibition. Taken together, these data suggest that CYP2D6*10/*10 individuals may be expected to require different drug doses; and show altered susceptibility to toxicity, interaction risk and, in the case of the amphetamines, drug dependence and toxicity compared to CYP2D6*1/*1 individuals.

 

[Soap MacTavish]

^good info.

For the 3rd day this technique produced longer duration again so I really doubt it's placebo. The whole timeline of amphetamine effects is stretched out. If you're after a bigger rush this might not work for you but if you're trying to push your supply farther or avoid W/D longer this might work.

 

[fastandbulbous]

The article says 'various amphetamines', but gives on info about how it metabolizes amphetamine. Yes other amphetamines would be N-dealkylated (not really surprizing that an O-dealkylator could also be an N-dealkylator), but amphetamine doesn't have any methyl groups to be removed