The cytochrome P450 superfamily (officially abbreviated as CYP) of enzymes are the major enzymes involved in drug metabolism and bioactivation, accounting for ~75% of the total metabolism.[1] Many drugs may increase or decrease the activity of various CYP enzymes by inducing or inhibiting their activity. This is a major cause of adverse drug interactions, since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels. The enzymes CYP2D6 and CYP3A4 are used to metabolize Dextromethorphan.[2]

Proportion of drugs metabolized by different CYP enzymes[3]

CYP2D6 is used to metabolize Dextromethorphan to Dextrorphan and 3-Methoxymorphinan to 3-Hydroxymorphinan.

[top]Inducers

· Piperidines and derivatives (pharmacokinetics modifiers)
· glutethimide (piperidinedione derivative)

[top]Inhibitors

Inhibitors of this enzyme will cause less DXM to be metabolized by CYP2D6 and decrease the amount of the more dissociating Dextrorphan.
Inhibitors of 2D6 include:
· quinidine (Zenvia contains dextromethorphan and quinidine).
· SSRIs (citalopram, fluoxetine and paroxetine)
· Some other antidepressants including bupropion and duloxetine
· terbinafine (antifungal)
· MDMA (Ecstasy)

CYP3A4 is used to metabolize Dextromethorphan to 3-Methoxymorphinan and Dextrorphan to 3-Hydroxymorphinan.

[top]Inducers

· phenobarbital (barbiturates)
· modafinil (stimulant)
· hyperforin (constituent of St Johns Wort)

[top]Inhibitors

When taken with DXM, inhibitors of enzyme CYP3A4 will cause more DXM to be metabolized by CYP2D6 and increase the amount of the more dissociating Dextrorphan.
Inhibitors of 3A4 include:
· grapefruit juice
· protease inhibitors (ritonavir, indinavir and nelfinavir)
· quercetin (nutritional supplement)
· SSRIs (fluoxetine/norfluoxetine and fluvoxamine)

^ Guengerich FP (January 2008). "Cytochrome p450 and chemical toxicology". Chem. Res. Toxicol. 21 (1): 70–83. http://dx.doi.org/10.1021%2Ftx700079z
^ "Comparative Contribution to Dextromethorphan Metabolism by Cytochrome P450 Isoforms in Vitro: Can Dextromethorphan Be Used as a Dual Probe for Both CYP2D6 and CYP3A Activities?" Retrieved on May 23, 2010. http://dmd.aspetjournals.org/cgi/con...ull/29/11/1514.
^ doctorfungus > Antifungal Drug Interactions Content Director: Russell E. Lewis, Pharm.D. Retrieved on May 23, 2010 http://www.doctorfungus.org/thedrugs...nteraction.htm

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[top]Inducers

[top]Inhibitors

[top]Inducers

[top]Inhibitors