Posted by Sad Panda on August 23, 2004, at 6:53:53
In reply to Re: P450-CYP2D6 » Sad Panda, posted by chemist on August 23, 2004, at 6:44:08
> > Hi All,
> >
> > Found this interesting at Pubmed
> >
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11304901
> >
> > "Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe.
> >
> > Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM.
> >
> > Wyeth-Ayerst Laboratories, 240 North Radnor-Chester Road, St. Davids, PA 19087, USA.
> >
> > Two antidepressants, venlafaxine and fluoxetine, were evaluated in vivo for their effect on cytochrome P450 2D6 (CYP2D6) activity, measured by the ratio of dextromethorphan, a sensitive CYP2D6 marker, to its metabolite dextrorphan (i.e., DM:DT) excreted in urine after DM coadministration. Twenty-eight healthy extensive metabolizers of CYP2D6 received either venlafaxine (37.5 mg bid for 7 days, then 75 mg bid until Day 28) or fluoxetine (20 mg daily for 28 days); 26 completed the study. Plasma concentrations of both drugs and their active metabolites were determined. DM:DTs were evaluated at baseline (Day 0), on Days 7 and 28 of dosing, and 2 weeks after drug discontinuation (Day 42). Steady-state drug and metabolite levels were achieved in both groups by Day 28. Mean DM:DTs for venlafaxine and fluoxetine differed statistically significantly (p < 0.001) on Days 7, 28, and 42. Comparisons of DM:DT as a percentage of baseline values showed that DM:DT increased 1.2-fold for venlafaxine and 9.1-fold for fluoxetine on Day 7 (p < 0.001) and increased 2.1-fold for venlafaxine and 17.1-fold for fluoxetine on Day 28 (p < 0.001). Inhibition of CYP2D6 metabolism persisted for 2 weeks after discontinuation of fluoxetine, unlike the case with venlafaxine. These in vivo results confirm in vitro data demonstrating significantly weaker inhibition of CYP2D6 with venlafaxine than with fluoxetine. This suggests that clinically significant interactions involving CYP2D6 inhibition could occur between fluoxetine and drugs metabolized by CYP2D6 but may be less likely to occur with venlafaxine."
> >
> > A 9x increase of dextromethorphan caused by fluoxetine is rather awesome & scary. I think I read somewhere that Paxil & Luvox are just as bad.
> >
> > For my original dilemma of adding nortriptyline to venlafaxine I have found that I had to lower my intake of venlafaxine which was painfull for awhile because we don't have 37.5mg capsules here.
> >
> > Cheers,
> > Panda.
> >
> >
> hi panda.....as for luvox, increased serum levels of DXM are reported in the prescribing information, but fluvoxamine is a weak inhibitor of 2D6: it is a potent substrate, however, of 2D6 and 1A2, and a potent inhibitor of 1A2. i would suspect that serum levels of DXM and metabolites via the 2D6 route would not be significantly enhanced by fluvoxamine as they are by fluoxetine, although i have no personal experience with DXM and luvox (xanax, dexedrine, caffeine/theophylline/theobromine, ambien, and several 1,4-benzos are fine with luvox, in my experience, past and present).....cheers to you, chemist
>
>Hi there chemist,
When you say fluvoxamine is only a weak inhibitor of 2D6, where would it fall between velafaxine at 1.2x & fluoxetine at 9.1x?
Cheers,
Panda.
poster:Sad Panda
thread:363939
URL: http://www.dr-bob.org/babble/20040821/msgs/381163.html