Posted by Larry Hoover on March 2, 2005, at 14:42:49
In reply to Drug interactions q., posted by banga on March 2, 2005, at 8:11:17
> Can anyone clarify/affirm this? Sort of an obvious question, but the med interaction descriptions on rxlist.com and drugs.com in my mind were not completely clear in their wording:
>
> IN the literature, it SEEMS that Luvox inhibits a particular enzyme, and increases the levels of Abilify; my guess is that they are assuming it does although they have no direct proof and that is why it is stated in an unclear manner?
>
> And it is also inclear to me whether levels of Luvox are also then elevated in parallel to the Abilify (is there competition for this enzyme, or does Luvox simply and directly inhibit the enzyme? (CYP450?? Maybe it's my braing fog, but just could not understand the relationship between these drugs and enzymes)
>
> And a related q. 2?: the lit also does say clearer that Luvox will raise desipramine levels; do then blood levels of Luvox also go up when taking desipramine?
>
> Anyone have the patience to understand my question ? The short version is: what are the effects of taking desipramine, Luvox and Abilify together?Sure. Lots of patience. All of the enzymes (number/letter/number) are members of the class of enzymes known as cytochrome P450 (CYP450) enzymes.
Fluvoxamine (Luvox) has three routes of metabolism (elimination), via enzymes 1A2, 2C9, and 2D6.
Desipramine uses 1A2 and 2D6.
Aripiprazozole (Abilify) uses 2D6 and 3A4.
You can see that all three are substrates for the 2D6 enzyme, so there will be direct competitive effects. Each will slow the other down in its use of 2D6, just like a line-up at a ticket window. You will also note, however, that each has alternate pathways to elimination, so the dependency on 2D6 is a little bit reduced. 2D6 also has an incredible broad range of functionality, based on genetic factors, so losing some 2D6 activity can be a big deal, or it could be trivial.
The other way drugs interact is by inhibition or induction. Fluvoxamine inhibits five different enzymes (1A2, 2C9, 2C19, 2D6, and 3A4), and desipramine inhibits 2D6. Abilify doesn't appear to inhibit or induce other enzymes.
It's safe to assume that all three drugs would have some mutual inhibition on their individual clearance rates, leading to higher than normal blood levels, for increased periods of time (i.e. lengthened half-lives). That is compensated for by titrating to lower therapeutic dose levels. Adding e.g. Abilify to an existing desipramine/fluvoxamine regimen might require slight dose reductions in the latter two, to avoid side effects (as an example). It's all about titrating to tolerable levels which are still efficacious. Taking maximum doses of any of them would not be a good idea, generally.
Lar
poster:Larry Hoover
thread:465379
URL: http://www.dr-bob.org/babble/20050227/msgs/465506.html