There has been a significant amount of research over the years to characterize CYP450 enzymes and uncover any polymorphisms that have clinical significance. This course will not discuss CYP450s at length, but we will consider CYP2D6 as one example:
- It is estimated that about 25% of common drugs are metabolized by CYP2D6.
- CYP2D6 accounts for only about 1% of all CYP450 enzymes, but it is vital in metabolizing about 100 drugs.
- There are more than 80 genetic variants have been described in the CYP2D6 gene. The normal, wild-type allele displays normal metabolic activity, whereas some variant forms have enhanced or diminished activity.
- The variants can be grouped generally according to the resulting alterations in protein function.
- The groupings correlate with four major enzyme metabolic capacities (phenotypes):
- poor metabolizers
- intermediate metabolizers
- extensive (normal) metabolizers
- ultra-rapid metabolizers
