Much research has been done on CYP450 enzymes and many polymorphisms with clinical significance have been identified. This course will not discuss CYP450s at length (for more see the course on Drug Metabolism) 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 important in the metabolism of about 100 drugs.
- There are more than 80 genetic variants that have been described in the CYP2D6 gene. The normal, wild-type allele displays normal metabolic activity whereas some of the 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