Raso, 10 mg 30 pcs.

Pharmacodynamics

Mechanism of action

Rabeprazole belongs to the class of antisecretory drugs which are chemically substituted benzimidazoles. Rabeprazole inhibits the activity of the enzyme H+/K+ATPase (“proton pump”), thus blocking the final stage of hydrochloric acid synthesis. This effect is dose-dependent and leads to inhibition of both basal and stimulated hydrochloric acid secretion regardless of the irritant.

Rabeprazole has no anticholinergic properties.

Antisecretory activity

After oral administration of 20 mg rabeprazole the antisecretory effect occurs within one hour. Inhibition of basal and stimulated hydrochloric acid secretion 23 h after the first dose of rabeprazole is 62% and 82%, respectively, and continues until 48 h. This duration of pharmacokinetic action is much longer than that predicted by the half-life (T1/2), which is approximately 1 h. This effect can be explained by the binding of the drug substance to the H+/K+ATPase of the gastric parietal cells. The magnitude of rabeprazole inhibitory effect on acid secretion reaches a plateau after three days of taking rabeprazole. On discontinuation of rabeprazole secretory activity is restored within 1-2 days.
Effect on serum gastrin concentration

At the beginning of therapy with rabeprazole serum gastrin concentration increases, which is a reflection of the inhibitory effect on hydrochloric acid secretion. Gastrin concentration usually returns to the initial level within 1-2 weeks after discontinuation of treatment.

Effect on enterochromaffin-like cells

A study of gastric fundus and intralesional biopsy specimens from more than 500 patients treated with rabeprazole or a comparison drug for up to 8 weeks showed no changes in the morphological structure of enterochromaffin-like (ECL) cells, gastritis severity, frequency of atrophic gastritis, intestinal metaplasia or prevalence of Helicobacter pylori infection.

In a study involving more than 400 patients receiving rabeprazole at a dose of 10 mg/day or 20 mg/day, lasting up to 1 year, the incidence of hyperplasia was low and comparable to that of patients receiving omeprazole at a dose of 20 mg/day. No cases of adenomatous changes or carcinoid tumors observed
in rats were reported.

Other effects

There is currently no evidence that rabeprazole causes systemic effects on the central nervous system (CNS), cardiovascular and respiratory systems. When administered orally in dose of 20 mg during 2 weeks rabeprazole has no effect on thyroid function, carbohydrate metabolism as well as on concentrations in blood of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, secretin, glucagon, follicle stimulating hormone, luteinizing hormone, renin, aldosterone and somatotropin.

Pharmacokinetics

Absorption

Rabeprazole is rapidly absorbed from the intestine and its maximum plasma concentration (Cmax) is reached approximately 3.5 h after a dose of 20 mg. Changes in Cmax and values of area under the pharmacokinetic curve “concentration-time” (AUC) of rabeprazole are linear in the dose range from 10 to 40 mg. Absolute bioavailability after oral administration of 20 mg (compared with intravenous administration) is about 52%. In addition, bioavailability does not change with repeated administration of rabeprazole. Neither the time of the drug intake within a day, nor antacids affect absorption of rabeprazole. Taking rabeprazole with fatty food slows down absorption of rabeprazole by 4 hours or more, but neither Cmax nor degree of absorption changes.

Distribution

In humans the degree of binding of rabeprazole to plasma proteins is about 97%.

Metabolism

Rabeprazole is metabolized in the body in two ways. Much of it is metabolized systemically by a non-enzymatic route with the formation of thioether derivatives. Rabeprazole is also metabolized in the liver via cytochrome P450 to form sulfonic and desmethyl derivatives.

In healthy volunteers, the plasma elimination half-life is approximately 1 h (range 0.7 to 1.5 h) and total clearance is 3.8 ml/min/kg.

Elevation

After a single oral administration of 20 mg of 14C-labeled rabeprazole, about 90% of rabeprazole is excreted by the kidneys, mainly as a carboxylic acid thioester, its glucuronide, and as mercapturic acid derivatives. Unchanged rabeprazole is not detected in the urine. The remaining part of rabeprazole taken is excreted through the intestine. Total excretion is 99.8%.

Terminal stage of renal failure

In patients with stable renal failure in the terminal stage who require maintenance hemodialysis (creatinine clearance <5 ml/min/1.73 m2), the excretion of rabeprazole is similar to that of healthy volunteers. AUC and Cmax in these patients were approximately 35% lower than in healthy volunteers. The average T1/2 of rabeprazole was 0.82 h in healthy volunteers, 0.95 h in patients during hemodialysis and 3.6 h after hemodialysis. Clearance of rabeprazole in patients with kidney disease requiring hemodialysis was approximately twice as high as in healthy volunteers.

Chronic compensated cirrhosis

Patients with chronic compensated cirrhosis tolerated rabeprazole well at a dose of 20 mg once daily, although AUC doubled and Cmax increased by 50%, compared with healthy volunteers.
Elderly patients

The elimination of rabeprazole is somewhat delayed in elderly patients. After 7 days of taking rabeprazole at a dose of 20 mg once daily, the AUC was approximately twice as high and Cmax was increased by 60%, compared to young healthy volunteers; no evidence of rabeprazole cumulation was noted.
CYP2C19 polymorphism

In patients with delayed metabolism via CYP2C19 isoenzyme after 7 days of taking rabeprazole at a dose of 20 mg daily the AUC increased 1.9 times and half-life increased 1.6 times compared to the same parameters in “fast metabolizers”, while Cmax increased by 40%.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

Concomitant use with digoxin may increase (mild to moderate) plasma concentrations of digoxin.

Concomitant use with ketoconazole decreases its bioavailability.

Special Instructions

Synopsis

Contraindications

Side effects

Pregnancy use

Similarities