Pantovaz Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Pantoprazole sodium sesquihydrate is a specific inhibitor of the gastric H+, K+-ATPase enzyme (the proton pump) that is responsible for gastric acid secretion by the parietal cells of the stomach. Pantoprazole is a substituted benzimidazole that accumulates in the acidic environment of the parietal cells after absorption. Pantoprazole is then converted into the active form, a cyclic sulphenamide, which binds selectively to the proton translocating region of the H+, K+-ATPase, thus inhibiting both the basal and stimulated gastric acid secretion. Pantoprazole exerts its effect in an acidic environment (pH < 3), and it is mostly inactive at higher pH. Its pharmacological and therapeutic effect is achieved in the acid-secretory parietal cells. As pantoprazole action is distal to the receptor levels, it can inhibit gastric acid secretion irrespective of the nature of the stimulus (acetylcholine, histamine, and gastrin).
In clinical studies investigating intravenous (i.v.) and oral administration, pantoprazole sodium inhibited pentagastrin stimulated gastric acid secretion. With a daily oral dose of 40 mg, inhibition was 51% on Day 1 and 85% on Day 7. Basal 24-hour acidity was reduced by 37% and 98% on Days 1 and 7, respectively.
Pharmacokinetics: Pantoprazole sodium sesquihydrate is rapidly variably absorbed following oral administration. Absorption is not affected by food. Pantoprazole is acid-labile and pharmacokinetics may vary between the various formulations developed to improve oral bioavailability. The absorption pantoprazole sodium as sesquihydrate also appears to be dose-dependent: increasing the dosage above 40 mg has been reported to increase the plasma concentrations in a non-linear fashion because of saturable first-pass hepatic metabolism. In addition, absorption is higher after a long-term administration. Bioavailability of Pantoprazole sodium sesquihydrate may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with impaired hepatic function, but is not markedly affected in patients with renal impairment.
Following absorption Pantoprazole sodium sesquihydrate is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19, to des-methylpantoprazole; small amounts are also metabolized by CY3A4, CYP2D6, and CYP2C9. Metabolites are excreted mainly (about 80%) in the urine, with the remainder being excreted in bile. The terminal elimination half-life is about 1 hour, and is prolonged in hepatic impairment: the half-life in patients with cirrhosis was 3 to 6 hours.