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عمومی::
متابولیزکنندهی فوق سریع
While we now have more detailed information on the genotypes, the phenotypic differences in CYP2D6 were originally observed with debrisoquine, resulting in the more general descriptions of poor metabolizer (PM), extensive metabolizer (EM), and ultrarapid metabolizer (UM) (Mahgoub et al, 1977; Idle et al, 1978).
The UM have very high rates of CYP2D6 enzymatic activity resulting in low plasma concentrations of drugs with consequent lower efficacy.
Active drugs like the tricyclic antidepressant amitriptyline may require doses several-fold higher than standard doses to achieve therapeutic activity when the patient is a UM.
Codeine is converted to morphine by a CYP2D6 O-demethylation reaction to provide analgesic effects, and morphine-associated toxicity has been reported after codeine administration in patients who are UM (Gasche et al, 2004).
The FDA label for codeine-containing products includes a black box warning to highlight the risk of death in children with CYP2D6 UM phenotypes.
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