Three main phenotypes have been identified that relate to the oxidative metabolisms of drug substrates by CYP2D6. The slow metabolizers (with defective CYP2D6 alleles), the normal metabolizers (wild type), and the ultra-rapid metabolizers all have variable number of genes for the functional CYP2D6 enzyme (13-15). Within the Caucasian population, approximately 7% of the CYP2D6 alleles are defective, resulting in potentially increased concentration of various drug metabolites at conventional therapeutic doses. Some of the most commonly used drugs, such as the beta-adrenoceptor blockers and tricyclic antidepressants, are substrates for CYP2D6 (13-15). The latter are known to cause adverse reactions that are attributed to increased levels of tricyclic antidepressants. These include, but are not limited to, such events as life-threatening arrhythmias and other cardiotoxic effects that result from decreased activity of CYP2D6 metabolism. Diagnostic tests are now available to identify beforehand those who are at risk.

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