Reloxa Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+, K+ ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, Rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion.
In gastric parietal cells, Rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide.
When studied in vitro, Rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds. It inhibits acid transport in porcine gastric vesicles with a half-life of 90 seconds.
Anti-secretory Activity: After oral administration of a 20 mg dose of Rabeprazole sodium, the onset of the anti-secretory effect occurs within one hour with the maximum effect occurring within two to four hours. Inhibition of basal and food stimulated acid secretion 23 hours after the first dose of Rabeprazole sodium are 69% and 82% respectively and the duration of inhibition lasts up to 48 hours. The inhibitory effect of Rabeprazole sodium on acid secretion increases slightly with repeated once-daily dosing, achieving steady state inhibition after three days. When the drug is discontinued, secretory activity normalizes over 2 to 3 days.
Serum Gastrin Effects: In clinical studies, patients were treated once daily with 10 or 20 mg Rabeprazole sodium, for up to 24 months duration. Serum gastrin levels increased during the first 2 to 8 weeks reflecting the inhibitory effects on acid secretion. Gastrin values returned to pre-treatment levels, usually within 1 to 2 weeks after discontinuation of therapy.
Pharmacokinetics: Rabeprazole is rapidly absorbed and peak plasma concentrations are reached about 3.5 hours after an oral dose.
The oral bioavailability is about 52% with the enteric-coated tablet formulation, because of first-pass metabolism, and does not appear to vary after single or repeated doses. Rabeprazole is about 97% bound to plasma proteins. It is extensively metabolised in the liver by cytochrome P450 isoenzymes CYP2C19 and CYP3A4 to the thioether carboxylic acid; sulfone and desmethylthioether. Metabolites are excreted principally in the urine (about 90%) with the remainder in the faeces. The plasma half-life is about 1 hour, increased two to threefold in hepatic impairment, 1.6 times in CYP2C19 slow metabolisers, and by 30% in the elderly.