CYP2D6

Metabolism via CYP2D6 is the major elimination pathway for numerous widely used medications, including beta-blockers such as carvedilol, metoprolol, and propranolol; antidepressants such as amitriptyline, desipramine, imipramine, and fluoxetine; and antipsychotics such as haloperidol and risperidone.

The effect of the variable number of CYP2D6 functional alleles is shown in Figure 1.19 for the systemic exposure of nortriptyline. The higher the number of functional CYP2D6 alleles, the lower the systemic exposure that was observed after administration of the same 25-mg nortriptyline dose to groups of subjects with different genotypes.

CYP2D6 is a highly polymorphic gene for which more than 70 variant alleles have been described. A series of genetic variants is responsible for low levels of CYP2D6 activity or no activity

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