Pantobex Mechanism of Action

Pharmacotherapeutic group: proton pump inhibitors. ATC code: A02BC02.
Pharmacology: Pharmacodynamics: Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific action on the proton pumps of the parietal cells. Pantoprazole is converted to its active form in the acidic canaliculi of the parietal cells where it inhibits the H+, K+-ATPase enzyme, i.e. the final stage in the production of hydrochloric acid in the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, freedom from symptoms is achieved in 2 weeks. As with other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole causes a reduced acidity in the stomach and thereby an increase in gastrin in proportion to the reduction in acidity. The increase in gastrin is reversible. Since pantoprazole binds to the enzyme distal to the cell receptor level, the substance can affect hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the product is given orally or intravenously.
Pharmacokinetics: General pharmacokinetics: Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single oral dose. On average at about 2.0 h-2.5 h p.a. the maximum serum concentrations of about 1-1.5 μg/ml (20 mg) and 2.3 μg/ml (40 mg) are achieved, and these values remain constant after multiple administration. Volume of distribution is about 0.15 l/kg and clearance is about 0.1 l/h/kg. Terminal half life is about 1 h. There were a few cases of subjects with delayed elimination. Because of the specific binding of pantoprazole to the proton pumps of the parietal cell the elimination half life does not correlate with the much longer duration of action (inhibition of acid secretion).
Bioavailability: Pantoprazole is completely absorbed after oral administration. The absolute bioavailability from the tablet was found to be about 77%. Concomitant intake of food had no influence on AUC, maximum serum concentration and thus bioavailability. Only the variability of the lag time will be increased by concomitant food intake.
Pantoprazole's plasma protein binding is about 98%. The substance is almost exclusively metabolized in the liver. Renal elimination represents the major route of excretion (about 80%) for the metabolites of pantoprazole; the rest are excreted in the faeces. The main metabolite in both the plasma and urine is desmethylpantoprazole, which is conjugated with sulphate. The half-life of the main metabolites (about 1.5 hours) is not much longer than that of pantoprazole.
Characteristics in patients/special groups of subjects: Although for patients with hepatic cirrhosis (classes A and B according to Child) the half-life values increased to between 3 and 6 hours and the AUC values increased by a factor of 3 to 5, the maximum plasma concentration only increased slightly by a factor of 1.3 compared with healthy subjects. Therefore the dose regimen in patients with hepatic cirrhosis should be reduced to one tablet every other day.
No dose reduction is required when pantoprazole is administered to patients with impaired kidney function (including dialysis patients). As with healthy subjects, pantoprazole's half-life is short. Only very small amounts of pantoprazole are dialysed. Although the main metabolite has a moderately delayed half-life (2-3 hours), excretion is still rapid and thus accumulation does not occur.
A slight increase in AUC and C_max in elderly volunteers compared with younger counterparts is also not clinically relevant.