CYP2D6-Mediated debrisoquine hydroxylation: genetic polymorphism
| Phenotype | Metabolic ratio2-a | Frequency | Genetic Basis | Possible Consequences |
|---|---|---|---|---|
| Poor metabolizer | Greater than 12 | 5%–10% Caucasian, 1%–2% Oriental | Gene deletion, mutation, frameshift or other defects; no protein or very poor enzyme activity. | Lower drug clearance and higher plasma level; exaggerated pharmacodynamic outcome and increased risk of concentration-dependent side-effects. |
| Ultrarapid metabolizer | Less than 0.1 | From 2% in a Swedish population to 30% in an Ethiopian population | About 40% carrying multiple copies of the CYP2D6 gene; mechanism of other ultrarapid metabolizers unknown. | Higher than normal doses required for efficacy; side-effects if metabolites are toxic. |
| Extensive metabolizer | Between 0.1 and 12 | Rest of the population | Large variations in metabolic ratio of this group; genetic basis for such a large variation unclear. | High or low end may need dose adjustment for acceptable efficacy and safety. |
↵2-a Metabolic ratio refers to the ratio of debrisoquine to 4-hydroxydebrisoquine in urine after oral dosing of subjects.