CYP2D6 Isoenzyme Metabolism

About 25% of all drugs used today are substrates for the CYP2D6 isozyme. This isozyme has been studied extensively. It greatly exhibits genetic polymorphism; certain individuals will lack this enzyme from birth as a result of an autosomal recessive defect in its expression. Individuals lacking CYP2D6 will have a much larger pharmacologic response to usual doses of drugs metabolized by this enzyme and will have a greater risk of adverse drug effects and/or toxicity. Conversely, prodrugs are usually inactive until enzymatic metabolism converts them to an active metabolite. Individuals will have little or no pharmacologic response to these drugs. CYP2D6 substrates include some tricyclic antidepressants, neuroleptics, antiarrhythmics, and b-adrenergic blockers. Inhibitors of CYP2D6 include tricyclics and SSRIs, and antiarrhythmics (particularly quinidine) and fluoxetine. CYP2D6 inducers include only a few drugs, primarily anticonvulsant agents. A more extensive listing of drugs involved with the CYP2D6 isoenzyme is shown in Table 2.

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