Pantor-20/Pantor-40/Pantor IV Mechanism of Action

Pharmacology: Pharmacodynamics: Pantor-20/Pantor-40: Mechanism of Action: Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg).
Pharmacokinetics: Pantor-20/Pantor-40: Pantoprazole sodium delayed-release tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (C_max) and area under the serum concentration time curve (AUC) increase in a manner proportional to oral and intravenous doses from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following oral or intravenous administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately one hour.
In extensive metabolizers with normal liver function receiving an oral dose of the enteric-coated 40 mg pantoprazole tablet, the peak concentration (C_max) is 2.5 mcg/mL; the time to reach the peak concentration (t_max) is 2.5 h, and the mean total area under the plasma concentration versus time curve (AUC) is 4.8 mcg·h/mL (range 1.4 to 13.3 mcg·h/mL). Following intravenous administration of pantoprazole to extensive metabolizers, its total clearance is 7.6 to 14.0 L/h, and its apparent volume of distribution is 11.0 to 23.6 L.
Absorption: After administration of a single or multiple oral 40 mg doses of pantoprazole sodium delayed-release tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and C_max was 2.5 mcg/mL. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute bioavailability of approximately 77%. Pantoprazole absorption is not affected by concomitant administration of antacids. Administration of pantoprazole sodium delayed-release tablets with food may delay its absorption up to 2 hours or longer; however, the C_max and the extent of pantoprazole absorption (AUC) are not altered. Thus, pantoprazole sodium delayed-release tablets may be taken without regard to timing of meals.
Distribution: The apparent volume of distribution of pantoprazole is approximately 11.0 to 23.6 L, distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin.
Metabolism: Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system.
Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity.
Elimination: After a single oral or intravenous dose of C-labeled pantoprazole to healthy, normal metabolizer volunteers, approximately 71% of the dose was excreted in the urine, with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged pantoprazole.
Special Populations and Conditions: Geriatric: Only slight to moderate increases in pantoprazole AUC (43%) and C_max (26%) were found in elderly volunteers (64 to 76 years of age) after repeated oral administration, compared with younger subjects.
No dosage adjustment is recommended based on age. The daily dose in elderly patients, as a rule, should not exceed the recommended dosage regimens.
Pediatric: The safety and effectiveness of pantoprazole for short-term treatment (up to eight weeks) of erosive esophagitis (EE) associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age appropriate formulation available. Therefore, pantoprazole is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of pantoprazole for pediatric uses other than EE have not been established.
Renal Impairment: In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects. No dosage adjustment is necessary in patients with renal impairment or in patients undergoing hemodialysis.
Hepatic Impairment: In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects. Although serum half-life values increased to 7 to 9 hours and AUC values increased by 5- to 7-fold in hepatic-impaired patients, these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal drug accumulation following once-daily, multiple-dose administration. No dosage adjustment is needed in patients with mild to severe hepatic impairment. Doses higher than 40 mg/day have not been studied in hepatically impaired patients.
Pantor IV: Absorption and Distribution: Following intravenous administration of Pantoprazole, serum/plasma concentrations decline biexponentially. The terminal half-life is about 1 hour. The total serum clearance is approximately 0.1/11/h/kg and the volume of distribution is about 0.15 L/kg.
The plasma kinetics for Pantoprazole after both oral and intravenous is linear over the dose range 10 to 80 mg.
Metabolism: Pantoprazole is almost exclusively metabolised in the liver. The main metabolite is desmethylpantoprazole, which is conjugated with sulfate.
Elimination: Renal elimination represents the most important route of excretion (approximately 80%) for the metabolite of Pantoprazole. The balance is excreted with faeces. The half-life of the main metabolite is approximately 1 and half hours which is slightly longer than that of Pantoprazole.