pharmacogenetic polymorphism

Pharmacogenetic polymorphism explains why the exact same dose can be too much for one person and too little for another. People inherit different versions of the genes that build metabolizing enzymes, so their drug-handling 'machinery' runs at different speeds from birth.

A polymorphism is a genetic variant common in the population. For drug-metabolizing enzymes, these variants sort individuals into groups such as poor, intermediate, extensive (normal), and ultra-rapid metabolizers. CYP2D6 and CYP2C19 are textbook examples, as are non-P450 enzymes like NAT2 (acetylation) and TPMT (thiopurine metabolism).

The clinical consequences cut both ways. A poor metabolizer of an active drug may accumulate it and suffer toxicity, whereas an ultra-rapid metabolizer may clear it too fast to benefit. For prodrugs the logic flips — poor metabolizers fail to activate the drug. These insights underpin pharmacogenomic testing and the move toward personalized, gene-guided dosing.