Aloe

Pharmacodynamics. Mechanism of action. Pantoprazole is a substituted benzimidazole that inhibits the secretion of hydrochloric acid in the stomach by specifically blocking the proton pumps of parietal cells. Pantoprazole is converted to its active form in the acidic environment within parietal cells, where it inhibits the enzyme H⁺/K⁺-ATPase, thereby blocking the final step of hydrochloric acid production in the stomach. This inhibition is dose-dependent and affects both basal and stimulated acid secretion. Most patients achieve symptom relief within 2 weeks. As with other proton pump inhibitors (PPIs) and H2-receptor antagonists, pantoprazole reduces gastric acidity and consequently increases gastrin secretion in proportion to the reduction in acidity. The increase in gastrin secretion is reversible. Since pantoprazole binds the enzyme distal to the cellular receptor, it can inhibit hydrochloric acid secretion regardless of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the drug is administered orally or intravenously. During pantoprazole treatment, fasting gastrin levels increase. With short-term use, they generally do not exceed the upper limit of normal. During long-term treatment, gastrin levels typically double. Excessive increases occur only in isolated cases. As a result, in a small number of cases during long-term treatment, a mild to moderate increase in specific endocrine (ECL) cells in the stomach is observed (similar to adenomatoid hyperplasia). However, according to studies conducted to date, the formation of carcinoid precursor cells (atypical hyperplasia) or gastric neuroendocrine tumors, which were observed in animal studies, has not been found in humans. Based on the results of animal studies, the influence of long-term pantoprazole treatment (exceeding one year) on thyroid endocrine parameters cannot be excluded. During treatment with antisecretory agents, serum gastrin levels rise in response to decreased acid secretion. Additionally, due to reduced gastric acidity, chromogranin A (CgA) levels increase. Elevated CgA levels may interfere with diagnostic investigations for neuroendocrine tumors. Available published data suggest that PPI therapy should be discontinued between 5 days and 2 weeks prior to CgA measurements. This allows CgA levels to return to the normal range, which may be falsely elevated following PPI treatment. Pharmacokinetics. Absorption. Pantoprazole is rapidly absorbed, and maximum plasma concentrations are achieved after a single oral dose of 40 mg. The maximum serum concentration of approximately 2–3 µg/mL is reached on average 2.5 hours after administration; concentrations remain stable after repeated dosing. Pharmacokinetic properties do not change after single or repeated administration. In the dose range of 10 to 80 mg, the plasma pharmacokinetics of pantoprazole are linear following both oral and intravenous administration. The absolute bioavailability of the tablets is approximately 77%. Concomitant food intake does not affect AUC (area under the concentration-time curve) or maximum serum concentration, and therefore does not affect bioavailability. Only the variability of the lag time increases with concomitant food intake. Distribution. Pantoprazole's serum protein binding is approximately 98%. The volume of distribution is approximately 0.15 L/kg. Biotransformation. The substance is metabolized almost exclusively in the liver. The main metabolic pathway is demethylation by CYP2C19 followed by sulfate conjugation; other metabolic pathways include oxidation by CYP3A4. Elimination. The terminal elimination half-life is approximately 1 hour, and clearance is 0.1 L/hr/kg. A few cases of delayed elimination have been noted. Due to pantoprazole's specific binding to the proton pumps of parietal cells, the elimination half-life does not correlate with the much longer duration of action (acid secretion inhibition). The majority of pantoprazole metabolites are excreted in the urine (approximately 80%), with the remainder excreted in the feces. The main metabolite in both serum and urine is desmethylpantoprazole conjugated with sulfate. The half-life of the main metabolite (approximately 1.5 hours) is not significantly longer than that of pantoprazole. Special patient populations. Poor metabolizers. Approximately 3% of Europeans lack functional CYP2C19 enzyme activity; they are referred to as poor metabolizers. In these individuals, pantoprazole metabolism is likely catalyzed primarily by CYP3A4. After a single 40 mg dose of pantoprazole, the mean area under the plasma concentration-time curve was approximately 6 times greater in poor metabolizers than in subjects with functionally active CYP2C19 (extensive metabolizers). Mean peak plasma concentration increased by approximately 60%. These findings do not affect pantoprazole dosing. Renal impairment. No dose reduction is recommended when pantoprazole is administered to patients with impaired renal function (including patients on dialysis). As in healthy individuals, the half-life of pantoprazole is short in these patients. Only very small amounts of pantoprazole are dialyzable. Although the main metabolite has a moderately longer half-life (2–3 hours), elimination is still rapid, so accumulation does not occur. Hepatic impairment. Although in patients with hepatic cirrhosis (Child-Pugh classes A and B) the half-life increases to 7–9 hours and AUC increases 5- to 7-fold, the maximum serum concentration increases only slightly — by a factor of 1.5 compared with healthy volunteers. Elderly patients. A slight increase in AUC and Cmax in elderly volunteers compared with younger volunteers is also of no clinical significance.