Genotyping for Functionally Important Human CYP2Dundefined4 (B) Mutation Using TaqMan Probes

The microsomal enzyme cytochrome P450 2D6 (CYP2D6), also known as debrisoquine 4-hydroxylase, is involved in the oxidative metabolism of many widely used drugs, including neuroleptics, tricyclic antidepressants, antiarrhythmics, and β-adrenergic blocking agents (1 ). Polymorphisms of CYP2D6 are the best characterized examples of genetically mediated effects on a drug-metabolizing enzyme of clinical importance (2 ). When a drug that is a CYP2D6 substrate is taken by different individuals, it is not uncommon to observe large differences in plasma concentrations at steady state. This is explained, in part, by the three clinically distinct phenotypes associated with the CYP2D6 gene, normal metabolizers, poor metabolizers, and rapid metabolizers. In normal metabolizers, steady-state plasma drug concentrations fall within the desired therapeutic range and toxic effects are nonexistent or minimal. In fast-metabolizer individuals, desired concentrations are below therapeutic, and these patients generally do not respond at the recommended dosing regimen. In poor-metabolizer individuals, drug concentrations are above therapeutic level and undesired toxicity can be evoked.