Pharmacological action - antiulcer.
It accumulates in the tubules of the parietal cells of the stomach and transforms into the active form - cyclic sulfenamide, which selectively interacts (forms a covalent bond) with the H + -K + -ATPase. It inhibits the H + -K + -ATPase of parietal cells, disrupts the transfer of hydrogen ions from the parietal cell into the lumen of the stomach and blocks the final stage of hydrophilic secretion of hydrochloric acid.
Dose-dependently suppresses basal and stimulated (regardless of the type of stimulus - acetylcholine, histamine, gastrin) secretion of hydrochloric acid. Values of the average effective dose for in vivo studies vary between 0.2–2.4 mg / kg. The maximum effect is manifested only in a strongly acidic (pH 3) medium (at higher pH values it remains practically inactive).
It has antibacterial activity against Helicobacter pylori and contributes to the manifestation of the anti-Helicobacter effect of other drugs. IPC is 128 mg / L. The therapeutic effect after a single dose occurs quickly and lasts for 24 hours. It provides a rapid reduction in symptoms and healing of duodenal ulcers. When taken at a dose of 40 mg, pH values> 3 persist for more than 19 hours. After 2 weeks of treatment (40 mg daily), complete healing of the duodenal ulcer is observed in 89% of patients. After 4 weeks of treatment (40 mg), 88% of patients have complete healing of the gastric ulcer. The recurrence rate of peptic ulcer after treatment is 55%.
Within 4 weeks of treatment at a dose of 40 mg / day, it provides complete remission in 82% of patients with gastroesophageal reflux disease of the II-III stage (according to Savary - Miller), after 8 weeks - in 92%. Complete endoscopic remission in 57% of children aged 6–13 years with gastroesophageal reflux disease of stage Ic / II (according to Vandeplas) is achieved after 4 weeks of therapy at a dose of 20 mg / day. Over the course of 4–8 weeks of treatment, the level of gastrin in the plasma rises 1.5 times. Supportive therapy (40–80 mg daily for more than 3 years) in patients with peptic ulcer was accompanied by a slight increase in the number of enterochromaffin-like (ECL-) cells.
Experimental studies of carcinogenicity indicate that prolonged use of pantoprazole is associated with an increased risk of ECL cell hyperplasia and the occurrence of gastric carcinoid, liver adenoma and carcinoma, and neoplastic processes in the thyroid gland.
Quickly and completely absorbed after oral administration. Absolute bioavailability of 70–80% (average 77%). Cmax - achieved after 2–4 hours (on average, after 2.7 hours). Plasma protein binding is 98%. T1 / 2 - 0.9–1.9 h, distribution volume - 0.15 l / kg, Cl - 0.1 l / h / kg. It penetrates very weakly through the BBB and is secreted into breast milk. Antacids or food intake does not affect AUC, Cmax, and bioavailability. The pharmacokinetics is linear in the dose range of 10–80 mg (AUC and Cmax increase in proportion to the dose increase).
The values of T1 / 2 and Cl are dose independent. It is metabolized in the liver (oxidation, dealkylation, conjugation). It has a low affinity for the cytochrome P450 system, mainly isoenzymes CYP3A4 and CYP2C19 are involved in metabolism. The main metabolites are demethyl pantoprazole (T1 / 2 - 1.5 hours) and 2 sulfated conjugates. It is excreted mainly in urine (82%) in the form of metabolites, and is found in small amounts in feces. Does not cumulate. T1 / 2 in patients with cirrhosis increases to 7–9 hours, with renal failure it increases slightly, but T1 / 2 of the main metabolite reaches 2-3 hours. AUC and Cmax are slightly higher in the older age group.
Peptic ulcer of the duodenum or stomach in the phase of exacerbation, including associated with NSAIDs, or refractory to therapy with histamine H2 receptor blockers; gastroesophageal reflux disease (moderate and severe); Zollinger-Ellison syndrome; combined anti-Helicobacter eradication therapy in patients with peptic ulcer in order to reduce the recurrence rate
Hypersensitivity, hepatitis and cirrhosis, accompanied by severe liver failure.
Pregnancy and lactation
During pregnancy, it is possible only under strict indications, when the benefit to the mother outweighs the potential risk to the fetus.
The FDA category of action for the fetus is B.
At the time of treatment should stop breastfeeding.
From the digestive tract: diarrhea; rarely - dry mouth, increased appetite, nausea, belching, vomiting, flatulence, abdominal pain, constipation, increased transaminase activity, gastrointestinal carcinoma (an isolated case).
From the nervous system and sensory organs: headache; rarely - asthenia, dizziness, drowsiness, insomnia; in some cases - nervousness, depression, tremor, paresthesia, photophobia, visual impairment, tinnitus.
From the genitourinary system: in isolated cases - hematuria, edema, impotence.
From the skin: in isolated cases - alopecia, acne, exfoliative dermatitis.
Allergic reactions: rarely - rash, urticaria, pruritus, angioedema.
Other: rarely - hyperglycemia, myalgia; in isolated cases - fever, eosinophilia, hyperlipoproteinemia, hypercholesterolemia.
May decrease pH-dependent absorption of ketoconazole and other drugs. It is compatible with drugs metabolized with the participation of the cytochrome P450 enzyme system: phenazepam, diazepam, digoxin, theophylline, carbamazepine, diclofenac, naproxen, piroxicam, phenytoin, warfarin, nifedipine, metoprolol, ethanol. Does not affect the effectiveness of hormonal contraceptives.
Symptoms: not described.
Treatment: for suspected overdose, supportive and symptomatic therapy is recommended. Dialysis is ineffective.
Before starting treatment, malignant diseases of the esophagus and stomach should be excluded (symptomatic improvement may delay the correct diagnosis and treatment). The diagnosis of reflux disease must be confirmed endoscopically. It is not recommended for patients with non-ulcer dyspepsia. In elderly patients and with impaired renal function, it is not recommended to exceed a dose of 40 mg / day. In severe liver failure, the dosage regimen should be adjusted: 1 table. every 2nd day, under the control of the level of liver enzymes (with its increase, drug withdrawal is indicated).