Cytochrome P450 2D6
Also known as: CYP2D6
Cytochrome P450 enzyme that metabolises about 20-25% of drugs, including many psychotropics, opioids and antiarrhythmics. It is highly polymorphic: there are poor, intermediate, extensive and ultrarapid metabolisers.
CYP2D6 inhibition (e.g. fluoxetine, paroxetine) can double concentrations of substrates such as codeine, tramadol and metoprolol; in poor metabolisers, prodrugs activated by this enzyme (codeine → morphine) may have reduced effect.
Substrates: codeine, tramadol, hydrocodone, metoprolol, carvedilol, timolol, flecainide, propafenone, haloperidol, risperidone, venlafaxine, fluoxetine, paroxetine.
Inhibitors: fluoxetine, paroxetine, bupropion, quinidine, ritonavir, cinacalcet.
Inducers: there are no clinically relevant inducers; activity depends mainly on genetics (CYP2D6 polymorphism).
Important in pain: codeine and tramadol depend on CYP2D6 to produce the active metabolite (morphine / O-desmethyltramadol); in poor metabolisers analgesia fails, in ultrarapid metabolisers there is a risk of opioid toxicity.
DailyMed/FDA (NIH/NLM) — approved labels (codeine, fluoxetine); PubMed (NIH/NLM) — CYP2D6 pharmacogenetics
