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CYP450 Induction and Inhibition

PGx is not the only factor to consider when thinking about variation in drug responses among different people. Although polymorphisms of drug-metabolizing enzymes are a big player, there are other big players that influence drug metabolism.

For example, many drugs are able to induce the expression of CYP450 enzymes (cause cells to produce more of a particular enzyme). Also, CYP450s can be inhibited by a variety of substances. For example, CYP2D6 can be inhibited by the common medications cimetidine (Tagamet) and fluoxetine (Prozac). Substances in food can also affect CYP450 expression or may simply compete with a drug for metabolism. An example is grapefruit. Several organic compounds found in grapefruit have an inhibitory action on CYP3A4.
Since many patients are on multiple medications and since dietary and environmental factors can change, CYP450 expression levels cannot be solely predicted based on their genotype.
Some CYP450 inducers and inhibitors are listed in the table on the following page.