CYP2D6 enzyme

Chen, S., et al., "The Cytochrome P450 2D6 (CYP2D6) Enzyme Polymorphism Screening Costs and Influence on Clinical Outcomes in Psychiatry," Clin. Pharmacol. Ther., 60, 522-534 (1996). 

Figure2.17 Percentage inhibition ofCYP2D6 plotted on thex-axis against compound stability (percent remaining, y-axis) after incubation with the CYP2D6 enzyme.

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes and also inhibits CYP3A4 and 2C9. Therefore, there are numerous potential drug-drug interactions to consider (Tables 49-3 and 49-4). The concurrent use of delavirdine with fosamprenavir and rifabutin is not recommended because of decreased delavirdine levels. 

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes. However, it also inhibits CYP3 A and thus inhibits its own metabolism. In addition to its interactions with other antiretroviral agents (see Table 49 1), delavirdine will result in increased levels of numerous agents (Table 49-3). Dose reduction of indinavir and saquinavir should be considered if they are administered concurrently with delavirdine. Delavirdine plasma concentrations are reduced in the presence of antacids, phenytoin, phenobarbital, carbamazepine, rifabutin, and rifampin concentrations are increased during coadministration with clarithromycin, fluoxetine, dexamethasone, and ketoconazole. 

Table 3 Some Drugs Whose Metabolism Is Catalyzed by the CYP2D6 Enzyme, i.e., the Debrisoquine/Sparteine Hydroxylase...

PROPAFENONE METOPROLOL, PROPANOLOL t plasma levels of propranolol and metoprolol Propafenone is extensively metabolized by CYP2D6 enzymes and interferes with the metabolism of propranolol and metoprolol Watch for propranolol and metoprolol toxicity 1 doses accordingly... 

Elimination Opioids are liepatically metabolized via the CYP2D6 enzyme into metabolite that are renally eliminated. The exception is methadone, which is metabolized via the CYP3A4 enzyme. 

The relationship between the CYP2D6 enzyme metabolic rate (phenotype) and the CYP2D6 genotype has been extensively characterized. Genetic variability accounts for the tetra-modal distribution of CYP2D6 activity described historically by the phenotypes. The rank order of... 

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