Posted by corafree on June 12, 2005, at 14:49:04 [reposted on June 12, 2005, at 17:29:14 | original URL]
In reply to Re: Metabolization Question » corafree, posted by Larry Hoover on June 12, 2005, at 11:26:37
Do we know which drugs need 2D6 and which do not?
Can a person be tested for their 2D6 enzyme?
I now promise ... I won't ask another question!
This has been an eye-opening education.
Did I tell you, one time I took Zoloft, felt a big surge of energy and optimism for about an hour; then fell back into depression and never again felt that relief w/ Zoloft?
One time I ate some bright green cooked spinach and felt that same surge. I guess Popeye was a true story! I am anemic; have been even long after having elective removal of birthing organs. Finally forked out $ for liquid iron accompanied by B vites; not pleasant to swallow!
So much for weekend; apologize if your relaxation or fun was curtailed! Dr. Bob and all are lucky to have you here! (And, I very sincerely mean that.) cf
> > Tks Lar.
> >
> > Just hit the wrong key and deleted my first response to your response.
> >
> > To begin with, thanks for taking your time to explain; though don't understand why you gave examples ... assuming the metabolite was not active. That would mean the 2D6 enzyme was not active, right?
>
> 2D6 is *the* enzyme usually involved in issues of poor to extensive metabolization of drugs. It is the only cytochrome enzyme that is not inducible. All the others can increase activity if their load increases. With 2D6, you get what God gave ya. In a fairly small sampling study I read, the 2D6 activity within a group was accurately measured. The variability within the group was 118-fold. That's 118 times, or 11,800% difference in metabolic rate between the poorest of the poor and the most extensive of the extensive metabolizers.
>
> An active metabolite is a converted form of the parent drug that itself has activity. In the case of Paxil and 2D6, you'd be looking at desmethylparoxetine. If desmethylparoxetine also has pharmacological activity, then the drug's effects include both premetabolism and post-metabolism effects. The true limiting factor then becomes elimination (via urine or feces).
>
> I gave two opposing examples. In the first instance a poor metabilizer had enhanced drug effects, whereas in the second example, the poor metabolizer had minimal drug effects. The extensive metabolizer, on the other hand, had minimal effects and maximal effects, respectively.
>
> > Am I correct in saying that a person cannot label themselves ALWAYS a 'poor metabolizer', 'normal metabolizer', or 'extensive metabolizer', ... because w/ one drug they may be a 'poor metabolizer', w/ another drug a 'normal metabolizer', and w/ another drug an 'extensive metabolizer'?
>
> As I say, this usually applies to 2D6 metabolism (I'm trying to simplify, and there are exceptions), and 2D6 activity is 100% genetically regulated (no environmental regulation of any sort; you get what you were born with). Therefore a poor metabolizer is a poor metabolizer of any drug that uses that same enzyme.
>
> The effects, though, don't just depend on the enzyme activity alone. Another factor to consider is the relative potency of the parent drug compared to its metabolites. A poor metabolizer can have minimal drug effect, or maximal, depending on this latter factor.
>
> > Lots of Tks, cf
>
> My pleasure,
> Lar
poster:corafree
thread:511635
URL: http://www.dr-bob.org/babble/20050611/msgs/511639.html