Slide 32 of 76
Notes:
- An enzyme inducer stimulate the production of more P450 enzymes. It does this by binding directly to promoter elements in the DNA region, resulting in an increase in P450 transcription (I.e., increase messenger RNA), and subsequently increase the amount of enzymes present. The presence of these additional enzymes results in a net increase in metabolic activity; the body is able to eliminate substrates more quickly, which results in a net reduction in substrate concentrations. Unlike inhibition, induction persists for several days, even after the inducing drug is gone. That’s because the enzymes persist for several days following induction.
- Enzyme induction is also influenced by age and liver disease. For instance, elderly patients, or those with cirrhosis or hepatitis may be less susceptible to enzyme induction.
- Inducers may also vary by specificity and potency:
- Some inducers are able to induce several types of enzymes. For instance, ritonavir induces the amount of CYP1A2 and glucuronyl transferase.
- Inducers also induce enzyme activity to varying degrees. For example, rifampin is a more potent inducer than rifabutin and as such, substrate levels are more likely to be reduced to a greater extent in the presence of rifampin versus rifabutin. For instance, nelfinavir concentrations are reduced by 32% with rifabutin, and by 82% with rifampin. Similarly, saquinavir concentrations are reduced by 40% with rifabutin, and by 80% with rifampin.
- Common classes of inducers include anticonvulsants and rifamycins
- Among antiretrovirals, nevirapine and efavirenz are potent enzyme inducers
