Pharmacogenomics: Why the Same Drug Works Differently for Everyone
Genetic variants in drug-metabolising enzymes mean that standard doses are wrong for many patients.
Pharmacogenomics is the study of how genetic variants influence an individual's response to medications. It explains why a standard dose produces therapeutic benefit in one patient, toxicity in another, and no effect in a third.
Drug-Metabolising Enzymes
The cytochrome P450 (CYP) enzyme family metabolises the majority of clinically used drugs:
- CYP2D6: metabolises antidepressants, antipsychotics, opioids. Poor metabolisers experience toxicity at standard doses.
- CYP2C19: metabolises clopidogrel and PPIs. Poor metabolisers on clopidogrel have significantly elevated cardiovascular event rates.
- CYP2C9 + VKORC1: dramatically affect warfarin dosing requirements.
Clinical Impact
Pre-emptive pharmacogenomic testing allows practitioners to select drugs for which a patient is a normal metaboliser, adjust doses based on metaboliser status, and avoid drugs associated with high risk. Full genome sequencing captures all pharmacogenomically relevant variants in a single test — a permanent record that informs prescribing decisions throughout a patient's lifetime.
