Omeprazole Metabolism, Mechanism of Action, and Sites of Drug-Drug Interactions and Genetic Polymorphisms
After absorption, omeprazole undergoes activation (protonation) and the activated cyclic sulfonamide irreversibly inhibits H+/K+–adenosine triphosphatase pump activity/gastric secretion. Omeprazole is extensively metabolized by and competitively inhibits CYP2C19 and CYP3A4. The major omeprazole metabolism pathway involves its conversion by CYP2C19 to inactive 5-hydroxyomeprazole that is metabolized to inactive omeprazole hydroxy sulfonate by CYP3A4 in the second step. However, omeprazole first metabolized by CYP3A4 to omeprazole sulfonate and further to omeprazole hydroxy sulfonate in the 2C19 loss-of-function allele carriers or subjects treated with drugs that are mainly metabolized by 2C19 such as clopidogrel, diazepam, and phenytoin. Abbreviations as in Figure 1.