Cytochrome P450 2D6 is involved in the metabolism of about 20-25% of clinically used drugs. Variation in its activity can significantly impact the required dosage, response to therapy and risk of adverse drug effects.
Patient Status
Phenotype (Activity of 2D6)
2 null alleleles with no functional activity
poor metabolizer (PM)
heterozygous with one partially deficient gene (some activity)
intermediate metabolizer (IM)
2 normal alleles
extensive metabolizer (EM)
alleles with multiple gene copies (greater than normal activity)
ultrarapid metabolixzer (UM)
About 5-10% of Caucasians are poor metabolizers based on 2D6 activity.
Drugs impacted by 2D6 include:
(1) dextromethrophan
(2) oxycodone
(3) tramadol
(4) venlafaxine
(5) morphine
(6) metoprolol
Activity of 2D6
Significance
poor metabolizer (PM)
responds to very low dose; may have toxic effects with a usual dose
intermediate metabolizer (IM)
responds to lower dose and/or prolonged dosing interval
extensive metabolizer (EM)
expected response with usual dose
ultrarapid metabolixzer (UM)
poor response at usual dose; requires high and frequent doses; toxic metabolites could be an issue
Differential diagnosis:
(1) nonadherence to overadherence
(2) drugs or chemicals interfering with 2D6 activity
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