Esomeprazole

When ATH:
A02BC05

Pharmacological action

Antiulcer agents – proton pump inhibitor, pravovrashtayushtiy omeprazole isomer. It reduces the secretion of hydrochloric acid in the stomach by specific proton pump inhibiting parietal cells. It is a weak base, and moving into the active form in the acidic environment of the secretory tubules parietal cells of the gastric mucosa, is activated and inhibits proton pump – фермент H⁺-K⁺-ATF canine. It inhibits both basal, and stimulated secretion of hydrochloric (salt) acid. The action comes after 1 hours after oral administration 20 mg or 40 mg. In daily use for 5 day dose 20 mg 1 time / day, the mean maximum concentration of hydrochloric acid after pentagastrin stimulation is decreased by 90%.

Pharmacokinetics

Unstable in acidic medium. In vivo, only a small portion of esomeprazole is converted into R-isomer. After ingestion is rapidly absorbed from the gastrointestinal tract. C_max plasma levels achieved after 1-2 no. The absolute bioavailability Repeated dose in the dose 20 mg 1 time / day – 89%. V_d – 0.22 l / kg. Plasma protein binding – 97%. Completely metabolized with participation of cytochrome P isoenzymes₄₅₀. The main part is metabolized with the participation of CYP2C19 to form hydroxy- and demethylated metabolites of esomeprazole. The metabolism of the rest of the CYP3A4 isoenzyme by another; with the formation of esomeprazole sulfoderivatives, which is the major metabolite, determined in plasma. All metabolites are pharmacologically inactive. In patients with active isoenzyme CYP2C19 (patients with active metabolism) systemic clearance – 17 l / h after a single dose and 9 l / – after multiple dose. T_1/2 – 1.3 hours at regular admission to the dosing regimen 1 time / day. AUC increases against the backdrop of multiple dose (nonlinear dependence of the dose and AUC at regular admission, that is a consequence of reduction in the metabolism “first pass” through the liver, as well as reducing systemic clearance, caused by inhibition of the enzyme CYP2C19 esomeprazole and / or its metabolite sulfosoderzhaschim). Not accumulates. Displays up 80% dose as metabolites kidneys (less 1% – in unchanged form), remainder – the bile.

In patients with inactive metabolism (1-2%) the metabolism of esomeprazole is mainly carried out with the participation of CYP3A4. At regular admission to the dose 40 mg 1 time / day, the mean AUC for 100% exceeds this value in patients with active metabolism. Averages C_max plasma in patients with increased metabolism inactive approximately 60%.

In severe hepatic insufficiency the metabolic rate is reduced, accompanied by an increase in AUC 2 times.

Testimony

Gastroesophageal reflux disease (GERD): erosive reflux esophagitis (treatment), prevention of relapse in patients with healed esophagitis, symptomatic treatment of GERD.

In the combined therapy: эрадикация Helicobacter pylori, duodenal ulcer, ассоциированная с Helicobacter pylori, prevention of relapse of peptic ulcers in patients with peptic ulcer disease, associated with Helicobacter pylori.

Dosage regimen

Is the inside. The dose is 20-40 mg 1 time / day. Duration of reception depends on the evidence, regimens, effectiveness.

In severe liver disease the maximum dose – 20 mg / day.

Side effect

Often: headache, stomach ache, diarrhea, flatulence, nausea, vomiting, constipation.

Rarely: dermatitis, itch, hives, dizziness, dry mouth.

Contraindications

Lactation, Hypersensitivity to ezomepromazolu.

Pregnancy and lactation

Data on the safety of esomeprazole in pregnancy. The use is possible in cases, when the expected benefit of therapy to the mother outweighs the potential risk to the fetus.

IN experimental studies animals did not reveal any direct or indirect negative impact on the development of the embryo or fetus. Introduction racemic material not exert any adverse effect on animals at gestation, during childbirth, and during postnatal development.

Cautions

If you have symptoms such as a significant spontaneous loss of body weight, frequent vomiting, dysphagia, vomiting of blood or melena, and if (or suspected) stomach ulcers should exclude the possibility of malignancy, as treatment with esomeprazole may cause symptoms and smoothing, thus, delay the correct diagnosis.

When long-term therapy should be regularly monitored the patient's condition.

During treatment with proton pump inhibitors gastrin levels in plasma increased as a result of the reduced secretion of hydrochloric acid intragastric. Patients, taking proton pump inhibitors for a long time, often marked the formation of cysts in the glandular stomach. These phenomena are caused by physiological changes as a result of inhibition of the secretion of hydrochloric acid.

Drug Interactions

It is believed, that, while the application may increase plasma concentrations and increased effects of imipramine, clomipramine, citalopram.

It is believed, that, while the application may decrease plasma concentrations and clinical efficacy of ketoconazole and itraconazole.

While the use of clarithromycin described a significant increase in AUC of esomeprazole due to inhibition of its metabolism under the influence of clarithromycin.

In an application may increase plasma concentrations of diazepam and phenytoin, what, apparently, no clinical significance.