Blatta Orientalis

Pharmacodynamics. Mechanism of action. Pantoprazole is a substituted benzimidazole that inhibits the secretion of hydrochloric acid in the stomach through specific blockade of the proton pumps of parietal cells. Pantoprazole is converted to its active form in the acidic environment of parietal cells, where it inhibits the H⁺/K⁺-ATPase enzyme, 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. Treatment with pantoprazole, as with other proton pump inhibitors (PPIs) and H2-receptor antagonists, 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 to 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. Fasting gastrin levels increase during pantoprazole therapy. 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. Excessive increases occur only in isolated cases. As a result, a small number of patients on long-term treatment develop mild to moderate increases in specific enterochromaffin-like (ECL) cells in the stomach (similar to adenomatoid hyperplasia). However, according to studies conducted to date, the formation of neuroendocrine tumour precursor cells (atypical hyperplasia) or neuroendocrine tumours of the stomach, as observed in animal studies, has not been reported in humans. Based on results from animal studies, an effect of long-term (more than one year) pantoprazole treatment on thyroid endocrine parameters 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 diagnostic investigations for neuroendocrine tumours. 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 reference range, which may be falsely elevated following PPI treatment. Pharmacokinetics. Absorption. Pantoprazole is rapidly absorbed, and peak plasma concentrations are achieved after a single oral dose of 40 mg. Maximum serum concentration of approximately 2–3 µg/mL is reached on average 2.5 hours after administration; this concentration remains constant after repeated dosing. Pharmacokinetic properties do not change after single or repeated administration. In the dose range of 10 to 80 mg, pantoprazole plasma pharmacokinetics 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 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 followed by sulphate conjugation; other metabolic pathways include oxidation by CYP3A4. Elimination. The terminal elimination half-life is approximately 1 hour, and clearance is 0.1 L/h/kg. A few cases of delayed elimination have been reported. 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 (acid secretion inhibition). 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. Poor metabolisers. Approximately 3% of the European population lacks functional CYP2C19 enzyme activity; these individuals are referred to as poor metabolisers. In these subjects, pantoprazole metabolism is probably mainly catalysed by CYP3A4. After a single dose of 40 mg pantoprazole, the mean area under the plasma concentration–time curve was approximately 6-fold greater in poor metabolisers than in subjects with functional CYP2C19 enzyme activity (extensive metabolisers). Mean peak plasma concentration was increased by approximately 60%. These findings do not affect the dosing recommendations for pantoprazole. 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 longer half-life (2–3 hours), excretion is still rapid and accumulation does not occur. Hepatic impairment. Although the half-life increases to 7–9 hours and AUC increases 5- to 7-fold in patients with hepatic cirrhosis (Child-Pugh classes A and B), maximum serum concentration increases only slightly — by a factor of 1.5 compared to healthy volunteers. Elderly patients. The slight increase in AUC and Cmax in elderly volunteers compared to younger volunteers is also not clinically significant.