Posted by Larry Hoover on July 14, 2008, at 14:02:52
In reply to Drug Metabolism Question, posted by LynneDa on July 14, 2008, at 9:21:23
> Quick Question: Drugs, in general, seem to stay in my system longer than they're supposed to. For example, one Benadryl makes me sleepy for a good 12 hours!
Diphenhydramine depends on enzyme 2D6, and to a lesser extent enzyme 3A4.
> .125 Halcion is supposed to get out of your system quickly, but I took it last night at 11pm.
Largely uses 3A4.
> It is now 9am and I can still feel the effects. I also take 20mg Lexapro at night
Escitalopram uses 3A4 and 2C19.
> and 300 mg of Wellbutrin, split between 2 pills per day.
Bupropion uses 2D6, and others.
> I know there are a lot of people out there in Babble-land with expertise and knowledge about pharmacology. Does anyone know why that is and if I can do something to change it?
Maybe 10% of the population has a defective 2D6 enzyme system.....either very weak, or even non-existent, activity. Any drug that depends on that enzyme for metabolism will have an extended, and often enhanced, effect. Moreover, the magnitude of the effect increases with repeated doses, as blood concentrations can rise substantially above normal levels due to low clearance rates.
Enzyme 3A4 is the most heavily used liver detox enzyme, and it can respond to demand by being upregulated (i.e. more of it is produced), although you can't count on that happening. However, drugs which use it must compete for whatever is present, and once again, enhanced effects can result.
In your case, based on pure supposition, I'd suspect that you have low 2D6 activity, and some moderate to heavy interaction at 3A4. Do not consume 3A4 inhibitors (e.g. grapefruit and/or its juice). You might also try lower doses of the drugs that are causing you problems. The lower dose might actually give you "normal" blood concentrations.
Lar
poster:Larry Hoover
thread:839650
URL: http://www.dr-bob.org/babble/20080706/msgs/839688.html