Calcium Aflofarm (o smaku truskawkowym)

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 of parietal cells, where it inhibits the enzyme H⁺-K⁺-ATPase, thereby blocking the final step of hydrochloric acid production in the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid secretion. Most patients become symptom-free within 2 weeks. Administration of pantoprazole, as with other proton pump inhibitors (PPIs) and H2-receptor antagonists, reduces gastric acidity and thereby increases gastrin secretion proportionally to the decrease in acidity. The increase in gastrin secretion is reversible. Since pantoprazole binds the enzyme distally 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 therapy, fasting gastrin levels increase. With short-term use, they do not exceed the upper limit of normal in most cases. During long-term treatment, gastrin levels double in most cases. An excessive increase occurs only in isolated cases. As a consequence, a slight to moderate increase in specific endocrine (ECL) cells in the stomach (similar to adenomatoid hyperplasia) is observed in a small number of cases during long-term treatment. However, according to studies conducted to date, the formation of neuroendocrine tumour precursor cells (atypical hyperplasia) or neuroendocrine tumours of the stomach, which were found in animal studies, has not been observed in humans. Based on results from animal studies, an influence of long-term (more than one year) pantoprazole treatment on endocrine parameters of the thyroid gland cannot be excluded. During treatment with antisecretory medicinal products, serum gastrin levels increase in response to reduced acid secretion. In addition, chromogranin A (CgA) levels increase due to decreased gastric acidity. Elevated CgA levels may interfere with investigations for neuroendocrine tumours. Available published data suggest that proton pump inhibitor 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 after PPI treatment. Pharmacokinetics. Absorption. Pantoprazole is rapidly absorbed, and maximum plasma concentrations are achieved even 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; the concentration remains at a constant level after multiple doses. Pharmacokinetic properties do not change after single or repeated administration. In the dose range of 10 to 80 mg, plasma pharmacokinetics of pantoprazole are linear after 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 hence bioavailability. Only the variability of the lag time increases with concomitant food intake. Distribution. Pantoprazole serum protein binding is approximately 98%. The volume of distribution is approximately 0.15 L/kg. Biotransformation. The substance is metabolised almost exclusively in the liver. The main metabolic pathway is demethylation by CYP2C19 with subsequent sulphate conjugation; other metabolic pathways include oxidation by CYP3A4. Elimination. The terminal elimination half-life is approximately 1 hour, and the clearance is 0.1 L/hr/kg. A few cases of delayed elimination have been noted. Due to the specific binding of pantoprazole to proton pumps of parietal cells, the elimination half-life does not correlate with the much longer duration of action (inhibition of acid secretion). The majority of pantoprazole metabolites are excreted renally (approximately 80%); the remainder is excreted in faeces. The main metabolite in both serum and urine is desmethylpantoprazole conjugated with sulphate. The half-life of the main metabolite (approximately 1.5 hours) is not much longer than that of pantoprazole. Special patient populations. Slow metabolisers. Approximately 3% of Europeans lack a functional CYP2C19 enzyme; they are called slow metabolisers. In these individuals, pantoprazole metabolism is probably mainly catalysed by CYP3A4. After administration of a single 40 mg dose of pantoprazole, the mean area under the plasma concentration-time curve was approximately 6 times greater in slow metabolisers than in subjects with a functionally active CYP2C19 enzyme (extensive metabolisers). The mean peak plasma concentration was increased by approximately 60%. These findings do not affect pantoprazole dosing. Renal impairment. No dose reduction is recommended when administering pantoprazole to patients with impaired renal function (including patients on dialysis). As in healthy subjects, the half-life of pantoprazole is short. Only very small amounts of pantoprazole are dialysed. Although the main metabolite has a moderately prolonged half-life (2–3 hours), elimination is still rapid and therefore accumulation does not occur. Hepatic impairment. Although the half-life increases to 7–9 hours in patients with hepatic cirrhosis (Child-Pugh classes A and B), and the AUC increases 5–7-fold, maximum serum concentration increases only slightly — by 1.5-fold compared to that in healthy volunteers. Elderly patients. A slight increase in AUC and Cmax in elderly volunteers compared with younger volunteers is also not clinically relevant.