RiteMED Pantoprazole Mechanism of Action

Pharmacology: Pharmacodynamics: Pantoprazole is a benzimidazole derivative that accumulates in the acidic environment of the parietal cells after absorption. It is then converted into the active form, a cyclic sulfenamide, which covalently binds to the (H+, K+)-ATPase enzyme system (proton pump) at the secretory surface of the gastric parietal cell. By acting specifically on the proton pump, pantoprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-dependent and leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus.
Pharmacokinetics: The onset of action of pantoprazole occurs within 15 to 30 minutes after a single dose of 20 to 120 mg IV and the duration of action is 24 hours.
Pantoprazole's apparent volume of distribution is 11 to 23.6 L. It is 98% bound to plasma proteins. Pantoprazole is extensively metabolized in the liver by the CYP450 enzyme system. The main metabolic pathway is demethylation by CYP2C19 with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4.
The total plasma clearance of pantoprazole is approximately 7.6 to 14 L/h after a single dose. The plasma elimination half-life is approximately 1 hour. Almost 71% of the metabolites are excreted in the urine while the remaining 18% are excreted in the feces via biliary excretion.
Special Populations: Poor Metabolizers: Approximately 3% of the Caucasian population lack a functional CYP2C19 isoenzyme and are called poor metabolizers. In such individuals, the metabolism of pantoprazole is probably mainly catalyzed by CYP3A4. After a single dose of 40 mg pantoprazole, the mean area under the plasma concentration-time curve (AUC) was approximately 6 times higher in poor metabolizers than in patients having a functional CYP2C19 enzyme (extensive metabolizers). The mean C_max values were also increased by 60%.
Elderly: There is a slight increase in AUC (43%) and C_max (26%) in elderly patients (64-76 years of age). The half-life of pantoprazole in the elderly is approximately 1.25 hours.
Hepatic Impairment: The half-life of pantoprazole is prolonged between 7 to 9 hours. The AUC is 5 to 7 times higher in patients with liver cirrhosis compared with healthy patients while the C_max is 1.5 times higher.