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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by saturn on May 11, 2006, at 14:21:58
The monograph says a lot about oxidation, glucoronidation and so forth...but is this via CYP450 metabolism? 2D6?
Posted by Larry Hoover on May 11, 2006, at 15:00:06
In reply to is modafinil metabolized by CYP450?, posted by saturn on May 11, 2006, at 14:21:58
>
> The monograph says a lot about oxidation, glucoronidation and so forth...but is this via CYP450 metabolism? 2D6?I'm not sure if we're reading the same monograph, or not, but the one I'm reading specifically mentions the enzymes, under drug-drug interactions.
http://www.rxlist.com/cgi/generic2/modafinil_cp.htm
At least 90% of the drug goes through CYP450, and yes, 2D6 is a major route. Note also that it induces 3A4, so you get the anti-grapefruit effect. It mentions 2C9, 2C19, also. Both of those have metabolic variants, like 2D6. This drug could be very different things to different people, depending on their genetic complement of CYP450 enzymes.
Lar
Posted by saturn on May 11, 2006, at 19:15:10
In reply to Re: is modafinil metabolized by CYP450? » saturn, posted by Larry Hoover on May 11, 2006, at 15:00:06
>
> At least 90% of the drug goes through CYP450, and yes, 2D6 is a major route.Thanks Lar,
Is there any way of knowing approximately how much of a major route 2D6 is?
-sat
Posted by Larry Hoover on May 12, 2006, at 10:05:23
In reply to Re: is modafinil metabolized by CYP450? » Larry Hoover, posted by saturn on May 11, 2006, at 19:15:10
>
> >
> > At least 90% of the drug goes through CYP450, and yes, 2D6 is a major route.
>
> Thanks Lar,
>
> Is there any way of knowing approximately how much of a major route 2D6 is?
>
> -satIf you mean your specific case, your body, there is only one way. That would be to take radioactive modafanil, and then to analyse your urine and feces for the specific conjugates/metabolites. But what would that tell you? You'd have to know the physiological effect of each metabolite.
How much of a drug goes through 2D6 also depends on the capacity of competing enzymes. Everybody is different. If you have low 2D6 activity, the other ones pick up the slack, eventually. The half-life of the parent drug depends on the integrated rates of all pathways. And like I said, everybody is different.
In this case, modafanil has many routes out of the body. There are many holes in the bucket for modafanil to leak out of the body. If a drug has only one route out of the body, and that route is compromised, that's when you run into real problems. Or, when there are two routes, and the ratio of metabolites has a significant influence on how the drug is experienced by that individual. We are far from being able to predict individual metabolism for a specific drug, if that's where your questions are leading you.
Lar
Posted by saturn on May 13, 2006, at 13:39:39
In reply to Re: is modafinil metabolized by CYP450? » saturn, posted by Larry Hoover on May 12, 2006, at 10:05:23
This is the end of the thread.
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