Cytochrome P450 isoenzymes genetic polymorphism

Diphenhydramine inhibits the cytochrome P450 isoenzyme CYP2D6, which is responsible, in part, for the metabolism of metoprolol and some other beta blockers. CYP2D6 shows polymorphism, with some individuals lacking significant CYP2D6 activity (poor metabolisers), in whom diphenhydramine would have little or no effect. See Genetic factors , (p.4), for more on polymorphism. 

The main metabolic pathway for esomeprazole, lansoprazole, omeprazole, pantoprazole, and to a lesser extent rabeprazole, is through the cytochrome P450 isoenzyme CYP2C19. This isoenzyme is subjeetto genetic polymorphism, (see Genetic factors , (p.4), for a further explanation of polymorphism). The poor metaboliser phenotype for CYP2C19 is found in approximately 1 to 6% of Caucasians, 1 to 7.5% of Blacks and 12 to 23% of Oriental and Indian Asians. ... 

Hydrocodone bitartrate is administered orally, with excellent absorption from the gastrointestinal tract and a bioavailability of approximately 50-60%. Peak serum concentrations of hydrocodone occur after approximately 1.3 hours, with an elimination half-life of approximately 3.8 hours, in normal adults. It is prohahly metabolized mostly in the liver and primarily cleared via renal pathways. Similar to codeine and oxycodone, hydrocodone is known to undergo metabolism by the cytochrome P450 isoenzyme CYP2D6, genetic polymorphisms of which may explain some of the observed interindividual variation noted with its use. This enzyme converts hydrocodone to hydrom or phone, which displays significantly more avid binding for p receptors and may account for much of hydrocodone s clinical effect. Concurrent use of hydrocodone with medications known to induce or inhibit this isoenzyme may thus alter its efficacy and toxicity. 

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