Mechanism of action<unk> 's mechanism of action first involves getting absorbed into the parietal cells of the stomach, which are the cells that are responsible for secreting hydrochloric acid (HCl). At this point,<unk>  is inactive. However,<unk>  is then secreted into the secretory canaliculus of the parietal cells, which is the space from which acid secretion occurs. Here, acid secretion is mediated by the energy-dependent acid pumps, called hydrogen potassium adenosine triphosphatase (H+/K+ ATPase) pumps. These enzymatic pumps have cysteine amino acid residues. After being activated by gastric (stomach) acid to a reactive sulfenamide intermediate,<unk>  permanently binds the cysteine residues, forming covalent, disulfide bonds. This action fundamentally alters the configuration of the acid pump, thereby inhibiting its activity. Thus, acid can no longer be secreted into the gastric lumen (the empty space of the stomach), and the pH of the stomach increases (decrease in the concentration of hydrogen ions, H+). Due to the permanent inhibition of the individual proton pump that each molecule of<unk>  has bound to, acid secretion is effectively suppressed until new proton pumps are produced by the parietal cells.<unk> , like other medications in the same class, cannot inhibit the H+/K+ ATPase pumps found in lysosomes, a cellular organelle that degrades biological molecules, because the pumps found in these organelles lack the cysteine residues involved in<unk> 's mechanism of action. A unique feature of<unk> 's mechanism of action in inhibiting acid secretion involves its activation. The pKa (the pH at which 50% of the drug becomes positively charged) of<unk>  is around 5.0, meaning that it doesn't take a lot of acid to activate it. While this theoretically translates into a faster onset of action for<unk> 's acid-inhibiting effect, the clinical implications of this fact have yet to be elucidated. Pharmacokinetics<unk> 's bioavailability is approximately 52%, meaning that 52% of orally administered dose is expected to enter systemic circulation (the bloodstream). Once in the blood,<unk>  is approximately 96.3%-97% bound to plasma proteins. The biological half-life of<unk>  in humans is approximately one hour. It takes about 3.5 hours for<unk>  to reach the maximum concentration in human plasma after a single orally administered dose. Oral absorption is independent of the dose administered.<unk>  is extensively metabolized by the liver. 90% of the drug is rendered into metabolites by the liver, which are then excreted by the kidneys. 10% of the dose is excreted in the feces. The drug metabolizing enzymes primarily responsible for<unk> 's metabolism are CYP2C19 and CYP3A4. However,<unk>  is mainly metabolized through non-enzymatic reduction to a thioether metabolite. Some of<unk> 's metabolites include the following: a thioether carboxylic acid metabolite, a thioether glucuronide metabolite, and a sulfone metabolite. The most common metabolites excreted in the urine are the mercapturic acid conjugate and carboxylic acid. A diagram of<unk> 's phase I metabolism is shown below. Phase I metabolism of<unk> , drawn in ChemSketch. Pharmacogenetics The effect of<unk>  may vary based upon the genetics of the individual taking the medication. People may have differences in their capacity to metabolize<unk>  to an inactive metabolite. This may be mediated through genetic differences in the gene that encodes for the metabolic enzyme CYP2C19. For example, people that are poor CYP2C19 metabolizers (i.e. their version of CYP2C19 is less effective than average) will have trouble metabolizing<unk> , allowing the active<unk>  to stay in the body, where it can exert its effect, longer than intended. Conversely, extensive CYP2C19 metabolizers (i.e. the average metabolic capacity of CYP2C19) will extensively metabolize<unk> , as expected. The poor metabolizing CYP2C19 phenotype is found in roughly 3–5% of Caucasian people, and in 17–20% of people of Asian ancestry. In a study on men of Japanese ancestry, this has translated to an average increase of total drug exposure by 50–60% compared to men in the United States. However,<unk> 's metabolism is primarily non-enzymatic (it is often inactivated chemically, without the participation of the body's natural drug metabolizing enzymes). Therefore, while a person's CYP2C19 phenotype will affect<unk> 's metabolism, it is not expected to dramatically affect the efficacy of the medication.
Rabeprazole
Esomeprazole
Lansoprazole
Omeprazole
Dexlansoprazole
Tenatoprazole
Pantoprazole
Cimetidine