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Pharmacokinetics

Discussion in 'General Treatment' started by Nielk, Aug 15, 2012.

  1. Nielk

    Nielk

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    From Wikipedia

    I wonder if anyone is familiar with this.
    The reason why I became interested is because I started to look into the fact that different people metabolize medications at different rates - probably due to genetics. this might partly explain why different people react differently to specific medications and/or need different dosages.

    I believe that I might be a "fast oxidizer" and I base this conclusion on the fact that a few months ago, I had to detox from Klonopin - 3mg a day. I had a blood test taken the morning after I stopped taking it and it showed no
    level of Klonopin in my system. Whereas someone else in the same situation still had it show up 3 weeks later.

    I wonder how much of an effect a person's rate of medication metabolism has on the efficiency of the drug.
  2. richvank

    richvank Senior Member

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    Hi neilk.

    People do differ considerably in the rates at which they metabolize various drugs. This can be a problem, especially for the people who metabolize a drug more slowly than normal. When the drug companies do their Phase III testing of a new drug, they choose a dosage that will apply to most of the people, but there are always some who metabolize it more slowly. This dosage is recommended to the doctors, and that's how they prescribe it. But those who metabolize more slowly are overdosed. The concentration of the drug rises higher in their blood and stays high longer. There can be toxic effects from this. The FDA has recognized this, and several years ago they posted a notice about it, and encouraged the drug companies to publish which CYP450 enzymes for example, do Phase 1 metabolism of new drugs that are put on the market. This has been done more in recent years, but generally speaking, people do not have their CYP enzyme polymorphisms characterized. Tests are not offered for most of the CYP enzymes by the mainstream medical labs, and I don't think the insurance companies will pay for them. The drug companies are "off the hook" by publishing how the drugs are metabolized, but I don't think this info is being used as much as it probably should be.

    The Genovations Detoxigenomic Profile characterizes polymorphisms in detox enzymes, including 8 of the CYP450 enzymes.

    An additional problem occurs in ME/CFS in that the detox system becomes dysfunctional due to the depletion of glutathione. Glutathione helps to counter the oxidative stress generated in Phase 1 detox, and also conjugates toxins in one of the Phase 2 detox pathways. Thus, drugs generally don't work very well in treating ME/CFS if they are given at normal dosages, because they cannot be detoxed at normal rates from the body.

    Klonopin is metabolized by CYP3A4 and probably also CYP2C19. People who have fast versions of these enzymes can expected to break it down more rapidly, and vice versa.

    Best regards,

    Rich
    Jarod likes this.
  3. Nielk

    Nielk

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    Thanks Rich.

    This is a fascinating subject. I never thought of this. Could this be a reason why so many ME/CFS patients are so sensitive to medications?

    Could this explain why the Klonopin was not detected in my blood test - just a day later?

    Is there any way at all to test for CYP3A4 and CYP2C19?

    Thanks again for all the useful information you shower us with.

    Nielk
  4. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    You can read about this test here: http://www.gdx.net/core/one-page-test-descriptions/Detoxi-Genomic-Test-Description.pdf
  5. Nielk

    Nielk

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  6. Dreambirdie

    Dreambirdie work in progress

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    Hey Nielk--

    I am also a fast oxidizer and do HORRIBLY with the benzos.
  7. Nielk

    Nielk

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    Wow! How did you find out that you were a fast oxidizer?
  8. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    I haven't done this test. You can check the price on the website. Some Genova tests are covered by Medicare or other insurance--I don't know about this one. They will tell you on the phone.

    Probably quite a few here have done this test.

    Best,
    Sushi
  9. richvank

    richvank Senior Member

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    ***Hi, neilk.

    Thanks Rich.

    ***You're welcome.

    This is a fascinating subject. I never thought of this. Could this be a reason why so many ME/CFS patients are so sensitive to medications?

    ***Yes. If you look at the CureTogether.com ratings of CFS treatments, you can see that the drugs tend to be near the bottom:

    http://curetogether.com/chronic-fatigue-syndrome/treatments/

    Could this explain why the Klonopin was not detected in my blood test - just a day later?

    ***Maybe so.

    Is there any way at all to test for CYP3A4 and CYP2C19?

    ***Yes, Sushi gave you info about the Genovations Detox. profile. They are both on it. If you don't have SNPs that slow them down, that might explain your fast metabolism of Klonopin.

    ***Another thing is that some of the CYP enzymes are inducible. In other words, if you had been taking Klonopin for a long time, or at high dosage, the activities of the enzymes that metabolize it may have increased in response to that.

    Thanks again for all the useful information you shower us with.

    ***Best regards,

    ***Rich
  10. Dreambirdie

    Dreambirdie work in progress

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    I think it came out in a hair analysis. ... not sure tho.
  11. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    also i think when talking about half life of drugs, sometimes it can be misleading to mean how long its effects last. active life i think is what gets mixed up with it eg valium has a half life of approx 100hrs but its not active for that long as far as its effects on someone, i would estimate it works for about 4-6hrs. i think many other drugs are the same.
    Interesting topic.
    Nielk likes this.
  12. Nielk

    Nielk

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    Now that you mention this, I realize that I too had a hair analysis done and it showed too that I'm a fast oxidizer.

    I wonder what percentage of ME/CFS patients are?
  13. alex3619

    alex3619 Senior Member

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    The related field, pharmacogenomics, looks at genetic variations leading to different drug metabolisms. Its has its own journal. This is all standard stuff for modern pharmacy and pharmacology degrees, but was unheard of 30 years ago. Bye, Alex
  14. Nielk

    Nielk

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    Alex,

    Have you done any of this testing on yourself?

    Thanks,

    Nielk
  15. alex3619

    alex3619 Senior Member

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    Hi Neilk, no, I havent done this testing on myself except for some methylation genes. The whole thing about testing methylation genes, or any of them with respect to metabolism, is to be able to personalize medicine. Its still its infancy - not enough labs, not enough understood, too expensive, doctors don't always know how to interpret the tests. It will get better though, in all these areas. Bye, Alex
  16. roxie60

    roxie60 Senior Member

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    http://www.cypalleles.ki.se/ This link provides a drill down for various CYP genes but I am having trubs figuring out the SNPs and specific risk alleles. I think most have to be translated to the 23andME format. Anyway, hope it is helpful to those who can make sense and use it to identify gene, SNP and risk allele. If it makes sense to our biochem / epigentics folks maybe they can post a list of CYP with SNP and risk allele and potential impact on a person.
    helen1 likes this.

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