Rabeprazole

Pharmacological properties

mechanism of action. rabeprazole belongs to the class of antisecretory compounds, which by chemical structure refers to substituted benzimidazoles. the drug does not have anticholinergic properties and does not block H2 receptors, but inhibits the secretion of hydrochloric acid in the stomach by specifically inhibiting the enzyme h + / k + atphase on the secretory surface of parietal cells of the stomach. this enzyme system is considered an acid (proton) pump, and thus rabeprazole is classified as a proton pump inhibitor of the stomach, which blocks the final stage of hydrochloric acid synthesis. rabeprazole is converted into the active sulfonamide form by protonation and interacts with the available cysteine ​​residues of the proton pump.

Antisecretory activity. After oral administration of rabeprazole, the antisecretory effect develops after 1 hour and reaches a maximum after 2-4 hours. The degree of inhibition of basal and stimulated gastric secretion 23 hours after taking the first dose of rabeprazole is 62 and 82%, respectively, and the duration of this effect reaches 48 hours. the effect of rabeprazole is somewhat increased with daily daily use of 1 tablet per day, stable inhibition of secretion is achieved 3 days after the start of administration. After taking rabeprazole, the secretory activity of the stomach is restored within 2-3 days.

Effect on the concentration of gastrin in plasma. After taking rabeprazole at a dose of 10 or 20 mg once a day, the concentration of gastrin in the blood serum increases in the first 2–8 weeks of treatment, which contributes to the inhibition of hydrochloric acid secretion. The concentration of gastrin returns to its original level, usually within 1-2 weeks after discontinuation of treatment.

Other effects. To date, there is no data on the systemic effects of the central nervous system, cardiovascular and respiratory systems, which could be caused by taking rabeprazole.

Pharmacokinetics Absorption. The drug is available in the form of enteric-soluble capsules; absorption of the active substance begins in the intestine. Rabeprazole is rapidly absorbed in the intestines. The maximum concentration of rabeprazole in blood plasma is reached approximately 3.5 hours after taking the drug at a dose of 20 mg. The maximum concentration of rabeprazole in blood plasma and the AUC value are linear in the dose range from 10 to 40 mg. The absolute bioavailability after oral administration at a dose of 20 mg (compared with iv) is about 52%, largely due to the metabolism of the primary passage through the liver. The bioavailability of rabeprazole with repeated administration does not increase. In healthy volunteers, the plasma half-life is about 1 hour (0.7–1.5 hours), and the total clearance is 283 ± 98 ml / min. Meal and time during the day do not affect the absorption of rabeprazole.

Distribution. The degree of binding of rabeprazole to plasma proteins is almost 97%.

Metabolism and excretion. The main metabolites of rabeprazole, determined in blood plasma, are thioether (M1) and carboxylic acid (M6), and secondary metabolites present in low concentrations include sulfone (M2), dimethylthioether (M4) and mercapturic acid conjugate (M5). Only dimethyl metabolite (M3) has insignificant antisecretory activity, but it is not detected in blood plasma.

Indications

Peptic ulcer of the stomach and duodenum; gastroesophageal reflux disease (coat of arms); non-ulcer dyspepsia; for eradication of helicobacter pylori (in combination with appropriate antibacterial agents); Zollinger-ellison syndrome; chronic gastritis with increased acid-forming function of the stomach in the acute phase.

Application

With peptic ulcer of the stomach and coat of arms, 20 mg are prescribed 2 times a day.the duration of the course of treatment for peptic ulcer of the duodenum is 2-4 weeks, gastric ulcer - 2-8 weeks, with coat of arms - 4-8 weeks; maintenance therapy for coat of arms - 10–20 mg once a day for up to 12 months.

With non-ulcer dyspepsia, 40 mg is prescribed once a day or 20 mg 2 times a day for 2-3 weeks.

For eradication, Helicobacter pylori is prescribed as part of the corresponding complex therapeutic regimens with antibiotics (amoxicillin, clarithromycin, tetracycline), metronidazole, furazolidone and bismuth preparations, for example: Barol 20 mg 2 times a day + clarithromycin 500 mg 2 times a day + amoxicillin 2 times a day + amoxicillin 1 g 2 times a day for 7 days.

Barol 20 mg 2 times a day + clarithromycin 500 mg 2 times a day + metronidazole 500 mg 2 times a day for 7 days.

With Zollinger-Ellison syndrome, the initial dose of the drug is 60 mg / day, if necessary, the dose is increased to 120 mg / day (daily dose of 80 mg or more should be divided into 2 doses), the dose and duration of the course of treatment are determined individually.

In chronic hyperacid gastritis in the exacerbation phase, 40 mg are prescribed per day (1 capsule 2 times or 2 capsules 1 time per day) for 2-3 weeks.

Capsules can not be chewed or opened, they should be swallowed whole.

Contraindications

Hypersensitivity to rabeprazole, substituted benzimidazoles or other ingredients of the drug, pregnancy and lactation, childrens age.

Side effects

Barol is usually well tolerated by patients. side effects, as a rule, are mild and short-lived. the most common side effects from the gastrointestinal tract and liver can be diarrhea or constipation, abdominal pain, nausea, vomiting, flatulence, belching, rarely - increased activity of liver enzymes, taste disturbance, dry mouth.

On the part of the hematopoietic system, in some cases, leukopenia, thrombocytopenia are noted.

From the nervous system, dizziness, headache, agitation or drowsiness, depression are possible.

Allergic reactions are possible - skin rash, itching, angioedema, bronchospasm.

Other manifestations: pharyngitis, back pain, flu-like syndrome, myalgia, chest pain, sinusitis, spasms of the calf muscles, urinary tract infection, in isolated cases - weight gain, visual impairment, excessive sweating.

special instructions

Before starting the use of the drug, it is necessary to exclude the presence of a malignant neoplasm in the patient.

Caution is advised when starting the use of Barol in patients with severe impaired renal and hepatic function.

It is not prescribed for children, since there is no experience of its use in patients of this age group.

The safety of Barola during pregnancy has not been established. It was experimentally revealed that the drug can penetrate the placental barrier, so its use during pregnancy is contraindicated. It is not known whether rabeprazole passes into breast milk, therefore Barol should not be prescribed during breast-feeding.

It is unlikely that Barola will have a negative effect on the ability to drive vehicles and work with potentially dangerous machinery, but in case of drowsiness, it is recommended to refrain from this kind of activity.

In the case of the development of dermatological manifestations, the use of the drug should be discontinued.

Interactions

Rabeprazole, like other proton pump inhibitors, is metabolized by the enzymes of the cytochrome p450 system (cyp 450).

Rabeprazole causes a strong and lasting decrease in the secretion of hydrochloric acid in the stomach, therefore, it can affect the pharmacokinetics of drugs, the absorption of which depends on the pH of the gastric contents.

Reception of rabeprazole causes a decrease in the concentration of ketoconazole in blood plasma by 33% and an increase of 22% in the minimum concentration of digoxin.Thus, patients using these drugs with Barol should be under medical supervision to determine the need for dose adjustment.

In vitro, rabeprazole is metabolized by the CYP 2C9 and CYP 3A isoenzymes of the CYP 450 system. These studies suggest that Barol has a low ability to interact with other drugs; while its effect on cyclosporine metabolism is similar to that of other proton pump inhibitors.

Overdose

Symptoms: excessive sweating,

dizziness, headache, drowsiness, dry mouth, nausea, vomiting.

Treatment: specific antidote unknown. In case of an overdose, symptomatic and supportive treatment is necessary.

Storage conditions

In a dry, dark place at a temperature of no higher than 25 ° C.

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