Pantoprazole or Omeprazole: which is better and how they differ, reviews. Omeprazole or pantoprazole: sharp points of discussion What is the difference between omez and pantoprazole

Added: 23.04.2017

One of the most common gastroenterological pathological conditions is an increased content of hydrochloric acid in gastric juice (or hyperacidity). This condition is the basis of inflammation of the stomach or duodenum, as well as the formation of ulcerative lesions in them. Increased acidity can occur both due to non-infectious causes - systematic and / or severe stress and poor nutrition, and due to colonization of the gastric mucosa by the bacterium Helicobacter pylori (infectious cause).

In both the first and second cases, for the treatment of hyperacid conditions, drugs of the PPI group are used, that is, inhibitors proton pump. The most common drugs in this group are omeprazole (omeprazole) and pantoprozolo (pantoprazole). The mechanism of action of the drugs is the same - they inhibit the enzyme H + / K + -ATPase (or the “proton pump”), which ensures the flow of hydrogen into the stomach cavity. With a decrease in the amount of hydrogen, the concentration of hydrochloric acid in the stomach decreases and acidity normalizes. gastric juice. As a result, permanent damage to the mucous membrane is eliminated and it can fully recover.

So what is the difference between Omeprazene and Pantoprosolo?

Comparative characteristics of drugs - PPI 1 and 2 generations.

* That is, the amount of active substance that reaches the site of its action (in a specific case, to the parietal cells of the stomach).

** That is, how much the drug can reduce the pathologically increased acidity of gastric juice.

*** That is, the time during which the active substance will lose half of its therapeutic concentration.

Summary

Omeprazole has a more pronounced antisecretory effect (4 times stronger than pantoprazole). Omeprazole begins to act faster, but the therapeutic concentration active substance decreases more quickly.

Pantoprazole is a "softer" drug. Begins to act later and less pronounced inhibits the secretion of hydrochloric acid. But at the same time, pantoprazole retains a therapeutic concentration in the blood longer. It has antimicrobial activity that omeprazole does not have. Pantoprazole has a wider drug compatibility.

Of the two drugs, it is impossible to single out a leader, since each of them has its own advantages and disadvantages. In one clinical case, Omeprazen will be preferable for the patient, in another - Pantaprozolo. The exact selection of the drug depends on the individual characteristics of the disease and can only be qualified by an experienced gastroenterologist. In the absence of the opportunity to consult with a specialist, an independent selection of the drug is possible based on the above information.

Diseases associated with the digestive system torment a huge number of people of all age and social groups. This contributes malnutrition, bad environment and bad habits to which modern society is exposed. The pharmaceutical industry does not stand still and is actively developing new tools to combat diseases of the digestive system.

Proton pump inhibitors (such as omeprazole or pantoprazole) are a fairly large class of drugs used in the treatment peptic ulcer. Is there a difference between these analogues and how significant is it? To begin with, let's take a closer look at these tools in order to answer this question.

Before comparing the two drugs, let's understand a little about what each of them is.

Omeprazole is an active ingredient; on its basis, both the drug of the same name and are produced. Omeprazole acts in two ways: firstly, it reduces the acidity of gastric juice due to its neutralizing effect, and secondly, it suppresses the secretion of hydrochloric acid at the cellular level.

All this creates a favorable environment for the healing of erosions and damage to the mucous membrane of the stomach walls.

Indications for taking the drug are:

• stomach and duodenal ulcer;
• reflux esophagitis;
• symptomatic gastroesophageal reflux disease;
• dyspepsia, against the background of increased acidity;
• Zollinger-Ellison syndrome.

The drug begins to act half an hour to an hour after ingestion, the effect persists for a day. After the course of treatment is completed, acid production returns to its previous level in a few (up to five) days.

The process of removing the drug from the body creates an additional burden on the liver, so it is not recommended to take Omeprazole for people suffering from liver diseases.

Contraindications to taking is intolerance to the components of the drug, such as lactose or fructose; children under four years of age (children under eighteen only in especially severe cases by decision of the attending physician). Taking during pregnancy should be justified and weighed, since the safety of the drug for the unborn child has not been clinically proven.

Brief information about Pantoprazole

Although this drug belongs to the same group as Omeprazole, the active ingredient here is different - pantoprazole. The principle of action is absolutely identical to the work of "Omeprazole", the drug blocks the release of acid and lowers the level of acidity in the stomach. It is used in the treatment of gastric and duodenal ulcers, reflux esophagitis and Zollinger-Ellison syndrome.

The dosage, of course, is calculated individually, but on average it is 40 mg per day (depending on the form of release, this is one or two capsules). The maximum safe dose that health authorities prohibit exceeding is 80 mg per day.

The difference between drugs

In order to understand how these two medicines converge, and what is the difference, we will consider them in the context of their main characteristics.

Price and manufacturer

"Pantoprazole" is produced by the Russian pharmaceutical company "Canonpharma" and its cost is 200-300 rubles per package (depending on the dosage). "Omeprazole" is represented on the market by several manufacturers (Russia, Serbia, Israel), and its cost ranges from 30-150 rubles.

active ingredient

It has been proven that the indicator of the comparative intensity of the antisecretory effect of a proton pump inhibitor in omeprazole is higher than that of pantoprazole. At the same time, the time required for the substance to block the secretion of pantoprazole is almost three times longer than that of omeprazole.

Release form

Omeprazole is available in the form of hard gelatin capsules. "Pantoprazole" is produced in the form of coated tablets.

The time it takes for the drug to take effect

"Omeprazole" begins to act approximately half an hour to an hour after ingestion (the time may vary slightly in each individual case). "Pantoprazole" in order to reach the level of the highest concentration in the blood plasma takes about two to two and a half hours.

Contraindications

The list of contraindications for "Omeprazole" is quite short, includes intolerance to the components of the drug, pregnancy and lactation, children's age, as well as concomitant use with certain drugs. “Contraindications to taking Pantoprazole are:

• intolerance to the components of the drug;
• age less than 18 years;
• dyspepsia (neurotic genesis);
• malignant tumors in the gastrointestinal tract;
• one-time reception with the drug "Atazanavir".

Admission against the background of treatment with other drugs. Observation of patients taking "Omeprazole" showed that a long-term dose of 20 mg per day did not affect the concentration in the blood of substances such as caffeine, theophylline, diclofenac, naproxen, propranolol, ethanol, lidocaine and some others. It is undesirable to use the drug in parallel with agents whose absorption depends on the pH value, since Omeprazole reduces their effectiveness.

"Pantoprazole" works similarly. However, it can be taken by the following groups of patients without any risk:

• For diseases of cardio-vascular system. An example of drugs: Digoxin, Nifedipine, Metoprolol;
• With diseases of the gastrointestinal tract. An example of antibiotics: "Amoxicillin", "clarithromycin";
• Taking oral contraceptives;
• Taking non-steroidal anti-inflammatory drugs;
• For diseases endocrine system, an example of drugs: "Glibenclamide", "Levothyroxine sodium";
• In the presence of anxiety and sleep disorders, taking "Diazepam";
• With epilepsy, taking "Carbamazepine" and "Phenytoin";
• After transplantation, taking Cyclosporine, Tacrolimus.

Side effects

The list of possible negative reactions of the body to taking Omeprazole is quite wide, however, most of them occurred in isolated cases. Among the relatively common (less than 10% of appointments) are: lethargy, headache and digestive problems, such as stool disorders, nausea, vomiting, increased gas formation, abdominal pain.

Much less often, in less than 1% of cases, insomnia, dizziness, hearing impairment, allergic skin reactions, weakness, swelling of the limbs, brittle bones, and an increase in the level of liver enzymes in the blood can be observed.

As for "Pantoprazole", in less than ten percent of cases there are headaches, abdominal pain, problems with stools, and gas formation. Less frequently, in less than 1% of appointments there are problems with sleep, dizziness, blurred vision, allergic skin manifestations(redness, itching, rash), general weakness and malaise, nausea.

Overdose

Cases of reactions to an excess of "Omeprazole" were observed with the following symptoms: a state of confusion, decreased visual clarity, drowsiness, a feeling of dry mouth, headache, nausea, heart rhythm disturbance. An overdose of "Pantoprazole" was not observed. But the manufacturer recommends, in any case, apply symptomatic treatment. Hemodialysis in both cases shows low efficiency.

Summing up, we can say that the difference between Omeprazole and Pantoprazole is not very significant. Preparations differ in price, as well as the active ingredient. At the same time, the mechanism of their effect on the stomach is absolutely identical. "Omeprazole" has been used in pharmacology for much longer, how it affects the body is better studied.

In this case, there was no case of an overdose of "Pantoprazole", side effects when taking it occur less frequently. In any case, it is worth discussing with your doctor which medicine is more preferable in this particular case and not making any decisions on your own.

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PPIs, or proton pump inhibitors, belong to a group of pharmacological drugs used in the treatment of gastric pathologies. Medicines quickly eliminate the symptoms provoked by excessive production of hydrochloric acid. Modern representatives of PPIs are most effective: Rabeprazole, Omeprazole, Lansoprazole, Pantoprazole and. They are used as part of complex treatment various kinds gastritis and ulcerative lesions. Before prescribing proton pump inhibitors, the gastroenterologist examines the results of laboratory and instrumental research. When prescribing dosages and determining the duration of treatment, the doctor takes into account general state the health of the patient and the presence of diseases in the anamnesis.

Omeprazole is the best known member of the proton pump inhibitor group.

Features of pharmacological preparations

Antacids have long been used to raise the pH of gastric juice. When it enters the human body, the active ingredients of the drugs enter into a chemical reaction with hydrochloric acid. The resulting neutral products are excreted from the digestive tract with each bowel movement. But antacids have serious disadvantages:

• lack of long-term therapeutic action;
• inability to act on the underlying cause of the disease.

Therefore, the synthesis of the first representative of proton pump inhibitors () made a breakthrough in the treatment of ulcers and gastritis. If antacids help to reduce the level of already produced hydrochloric acid, then PPI prevents its production. This avoids the development of dyspeptic disorders in a person - excessive gas formation, nausea, vomiting, heartburn and acid belching. The undoubted advantage of proton pump inhibitors is the ability to maintain the maximum therapeutic concentration in the systemic circulation for a long time. Only after 15-20 hours, the parietal cells of the stomach begin to produce hydrochloric acid again.

It takes a different time to activate PPI representatives in the digestive tract:

• Rabeprazole has the fastest therapeutic effect;
• Pantoprazole has the slowest action.

There are proton pump inhibitors and general properties. For example, after penetration into the gastrointestinal tract, all PPIs inhibit the production of caustic acid by more than 85%.

Warning: “When choosing a drug for the treatment of gastritis or ulcerative lesions, doctors take into account the individual sensitivity of patients to the active substance of a particular proton form inhibitor. It manifests itself in a rather peculiar way - even with a recent intake of tablets, the pH of the gastric juice drops sharply. This concentration of acid is determined within about an hour, and then there is a sharp improvement in the well-being of a person.

The action of drugs in the human body

PPIs are precursors medicines. The therapeutic effect begins only after the addition of a hydrogen proton to them in the gastrointestinal tract. The active form of the drugs acts directly on the enzymes responsible for the production of hydrochloric acid. Proton pump inhibitors do not immediately begin to show their medicinal properties, but only as the accumulation of basic compounds in the tissues and their conversion into sulfenamides. The rate of decline in hydrochloric acid production may vary depending on the type of drug.

But such a difference is possible only in the first days of using PPIs. During the clinical research it has been proven that after a week of using any proton pump inhibitors, their therapeutic efficacy levels off. This is made possible by the similar chemical composition medicines. All PPIs are substituted benzimidazole derivatives and are formed by the reaction of a weak acid. After activation in the small intestine, the drugs begin to act on the glandular cells of the gastric mucosa. It happens like this:

• PPIs penetrate into the tubules of parietal cells, turning into tetracyclic sulphenamides;
• the proton pump contains cysteine ​​receptors, with which sulfenamides bind via disulfide bridges;
• the action of (H +, K +) -ATPases located on the apical membranes of glandular cells begins to be suppressed;
• slows down, and then completely stops the transfer of hydrogen protons into the stomach cavity.

After inhibition of (H +, K +) -ATPase, the production of hydrochloric acid by the cells of the gastric mucosa becomes impossible. Carrying out antisecretory therapy is indicated for patients with any form of gastritis, even with low acidity. This is necessary for the rapid regeneration of damaged tissues - the main cause of pain in the epigastric region.

Tip: “Don't skip PPIs or stop treatment. A prerequisite for rapid tissue regeneration is the constant presence of drugs in the human body. Healing and scarring of ulceration occurs several weeks after the start of proton pump inhibitors.

Proton pump inhibitors with pantoprazole increase the effect of antibiotics

All types of proton pump inhibitors

Gastroenterologists use five representatives of proton pump inhibitors for the treatment of gastrointestinal pathologies, which differ from each other in active ingredients. If one PPI fails, the doctor replaces it with another drug. On the shelves of pharmacies, each type of antisecretory agent is represented by many structural analogues of Russian and foreign production. They can have serious price differences, despite the same dosage and number of capsules.

When choosing between analogues of one of the PPI representatives, a gastroenterologist often recommends a more expensive drug to the patient. You should not accuse the doctor of any self-interest - such a preference is justified in most cases. For example, the Russian drug Omeprazole has analogues:

• Indian Omez;
• Ultop made in Slovenia.

Many patients will not feel a difference when taking these drugs, as they exhibit approximately the same therapeutic effect. But for some people, recovery will come after a course of treatment with Ultop. This is not only due to the quality active substance, but also various auxiliary ingredients used to form capsules and tablets. Proton pump blockers are drugs that require individual approach when prescribing dosages and duration of course treatment.

Lansoprazole

The bioavailability of this member of the PPI group approaches 90%. The mechanism of action of Lansoprazole differs from other drugs in the design of radicals that provide an antisecretory effect. The drug contributes to the formation of the formation of specific immunoglobulins to Helicobacter pylori. As a result, the growth of the Gram-negative bacterium is successfully suppressed. This proton pump inhibitor has no effect on gastrointestinal motility. Structural analogues of Lansoprazole include: Lancid, Epicurus, Lanzap.

Pantoprazole

Unlike other PPIs, Pantoprazole can be used for a long time in the treatment of gastritis and ulcerative lesions. This method does not lead to the development side effects. Pantoprazole is used regardless of the pH of the gastric juice, as this does not affect its therapeutic efficacy. The undoubted advantage of a proton pump inhibitor is the absence of diagnosed exacerbations of the disease after its course administration. Pantoprazole is available from manufacturers in the form of capsules for oral administration and injection solutions. The most famous structural analogues of the drug are Krosacid, Controloc, Nolpaza.

Rabeprazole

This anti-ulcer agent differs from omeprazole in the structure of the pyride and imidazole rings, which allows Rabeprazole to more effectively bind protons and potassium ions. The proton pump inhibitor comes in the form of enteric-coated capsules. After the use of Rabeprazole, ulcerative lesions are completely cured one month after the start of the drug. Gastroenterologists include the drug in the therapeutic scheme of gastritis provoked by Helicobacter pylori. Structural analogues of Rabeprazole include: Zolispan, Hairabezol, Beret.

Esomeprazole

Due to the presence of only one S-isomer, esomeprazole is not as rapidly metabolized by hepatocytes as other proton pump inhibitors. The drug is in the systemic circulation for a long time at the maximum therapeutic concentration. The therapeutic effect of esomeprazole lasts about 15 hours, which is the highest among all PPIs. The most famous analogues of this drug are Emanera, Nexium.

Benefits of Proton Pump Inhibitors

Manufacturers produce proton pump inhibitors in the form of capsules, tablets, solutions for parenteral use. Injectable drugs are used for exacerbation of gastric pathologies, when it is necessary to quickly reduce the production of hydrochloric acid. The active substances of solid dosage forms are coated with a strong shell. It is necessary to protect proton pump inhibitors from the effects of aggressive gastric juice. Without the shell, the main compound of the drugs would quickly collapse, without having time to have any therapeutic effect.

The presence of such protection ensures that the PPI enters the small intestine and the active substance is released in an alkaline environment. This route of penetration allows drugs to exhibit maximum therapeutic properties. The undoubted advantages of drugs include:

• fast and effective elimination of heartburn and epigastric pain in patients with increased production of gastric juice and digestive enzymes;
• longer and more intense reduction in hydrochloric acid production compared with antacids and H2 receptor antagonists;
• the highest efficiency in the treatment of patients with gastroduodenitis, gastric ulcer and duodenal ulcer;
• the presence of a short half-life and a slight renal clearance;
• rapid absorption in the small intestine;
• high level of activation even at low pH values.

Proton pump inhibitors are drugs that gastroenterologists always include in the therapeutic regimen if Helicobacter pylori has been detected in patients during laboratory tests. These gram-negative bacteria often cause ulcers and gastritis. Pathogenic microorganisms are equipped with flagella, with which they.

The drug Omeprazole is prescribed in cases of ulcers of the gastric surfaces and duodenum, with gastritis and gastropathitis. The function of the drug is to reduce the amount of hydrochloric acid in the stomach in case of a negative reaction of the patient to its excess. The active component of omeprazole compensates for the lack of vitamins and, interacting with stomach acid, leads to the destruction of the beginnings of peptic ulcer. The drug inhibits the production of hydrochloric acid, affecting its activity.

A characteristic feature of the remedy is that it begins to show its medicinal qualities only when it enters an environment with an acidic reaction characteristic of the stomach. The drug is able to eliminate the action of the causative agent of ulcerative diseases and gastritis, a microorganism called Helicobacter pylori.

The drug is available in the form of tablets, capsules, powder, the active components of its analogues are similar in principle to the original and have the same active ingredient - omeprazole. However, taking the drug has contraindications, the main of which are chronic liver diseases, as well as periods of lactation and pregnancy.

Taking a medicine

The use of the drug is made before eating food for breakfast or before dinner. The dosage of the medicine is strictly individual, is prescribed in accordance with the disease card and depends on the severity of the disease. An overdose of the agent can cause a change in taste sensations, a feeling of dryness in the oral cavity and its inflammation, unstable stools, vomiting, impaired liver function, various skin diseases, and affect the qualitative and quantitative composition of human blood.

Types of medication

A natural remedy, a drug produced by branded companies, on the basis of a legal basis consisting in the presence of a patent.

Generics, characterized in that they do not have patent protection for the product. Otherwise, according to the manufacturer's statements, confirmed by doctors, the drug is completely identical to the original.

Omeprazole's analogs

Ultop is made in Portugal and differs from the original in the production process and release form. Ultop is characterized by release in the form of 40 mg injectable powders and capsules, what is its difference from Omeprazole, produced in 20 mg capsules. It differs in the ultop and in addition to the main substances, among which sugar particles are contained complex composition and magnesium carbonate when the analogue contains titanium dioxide, glycerin and sodium lauryl sulfate. Despite the fact that the drugs are similar in indications for use, Ultop has an advantage over omeprazole, consisting in the fact that it can be prescribed to patients with impaired liver function. It is unacceptable to take Ultop, in addition to other contraindications, in case of a negative reaction of the body to sugar.

De-Nol acts on Helicobacter pylori, forming an astringent protective layer in connection with protein bodies in areas damaged by an ulcer. When taking De Nol, which has an antimicrobial effect, under the layer covering the surface of the mucosa, epithelial tissue is restored and scars are healed. De-Nol is able to penetrate deep into the mucous membrane, the habitat of bacteria of this species. The manufacturer of De-Nol is the Netherlands, the cost of a relatively cheap and affordable drug Omeprazole is high and ranges from 5 to 10 US dollars for 56 and 120 pieces, depending on the number of tablets, respectively. The main difference between De-Nol and the original is its antibacterial effect, which is carried out by changing the conditions for the presence of microorganisms and through a direct bactericidal effect.

Ranitidine

Ranitidine counteracts the emergence of neurotransmitter chains for pain impulses, reduces the amount of hydrochloric acid in the body and has the effect of suppressing peptic ulcers. Indications for taking ranitidine are the critical stages of gastric ulcers, increased acidity in gastritis, surgical actions with the stomach. The difference between the original drug and Ranitidine is that Omeprazole performs the functions of blocking the production of acid and eliminating excess acid, which contributes to the recovery processes. Another feature of Ranitidine is the addiction of the body to the doses of the drug, which provokes their increase, unlike the original.

Pantoprazole

Pantoprazole is characterized by a high activity of its biological components with a lower effect of suppressing acid production than that of Omeprazole. At the same time, the cost of Pantoprazole starts from US$ 3.5, while the price for Omeprazole is at the level of $ 0.5-3.5. Since the analogue of Omeprazole Pantoprozol has a longer disintegration time, it is better to practice a one-time administration of the drug during the day. The difference between the drugs and that Pantoprozol can be taken during the pregnancy period. A feature of the drug Pantoprozol is its inherent bactericidal properties.

Nolpaza

Despite the same purpose and rather high efficiency of Nolpaza in reducing the production of hydrochloric acid, it is not recommended to independently change the prescribed original drug to an analogue. Nolpaza, in comparison with Omeprazole, shows a greater bioavailability of the components of the agent, however, in the treatment of peptic ulcer, it is more preferable to take Omeprazole. Nolpaza shows good clinical results when used in complex treatment. The form of release of the Nolpaza analogue drug, which is produced in the form of oval-shaped tablets, and not capsules like Omeprazole, differs from the original one. It is not possible to identify, according to patients' reviews, the answer to the question of which drug is better to take, since Nolpaza, like Omeprazole, show equally high efficiency depending on the indications for treatment.

Emanera

The drug Emanera is characterized by the suppression different forms production of hydrochloric acid, by directional action. Emaner's remedy is characterized by the rapid achievement of an antisecretory effect. Based on this, taking Emanera is recommended with strict adherence to the dosage prescribed in the prescription of the drug by the doctor. The price of the Slovenian drug Emanera is $7 for 28 capsules with a total weight of 20 mg of the active substance.

Esomeprazole

Esomeprazole is a separate substance at the molecular level that mimics omeprazole. Esomeprazole is the active ingredient of the previously discussed drug Emaner. Despite this, Esomeprazole has many side effects that occur after administration: constipation, depression, drowsiness, taste changes and various skin diseases. In general, it can be said that when exposed to Helicobacter pylori, no visible difference in action was found between Esomeprazole and Omeprazole, with the analogue being more effective in the treatment of GERD. However, the benefits of Esomeprazole are offset by contraindications and a fairly high price compared to the analogue.

Pariet

Means Pariet is characterized by a higher rate of exposure, elimination of the symptoms of the disease compared to Omeprazole. At the same time, Pariet causes fewer side effects that pass in a milder form than the original remedy. However, on the basis of this, one should not conclude that it is possible to replace the original with an analogue of Pariet, this decision is within the competence of the attending physician. Pariet also shows high efficiency in reducing acidity, compared with Omeprazole. The price of the drug Pariet is also high compared to Omeprazole and is about 10 US dollars for 7 pieces of the drug.

Lansoprazole

Lansoprazole is identical to Opeprazole, except for the higher speed of the first drug. In the issue of suppressing the production of hydrochloric acid, there is a particular difference between the effectiveness of Lansoprazole and original drug not noticed. Lansoprazole, based on the action it has when it enters the small intestine, is available in capsules with fine granules. Distinctive feature Lansoprazole is also capable of rapid healing of gastric ulcers. To possible side effects The drug Lansoprazole treats belching, heartburn, dysbacteriosis, constipation.

Losek

Losek is a form of the official analogue of Omeprazole produced by an Austrian company. The active substance of the drug Losek is a multitude of omeprazole magnesium granules encapsulated, acting locally to suppress acid secretion. The Losek preparation is activated, exclusively being in an environment with a certain acidic background, that is, exactly at the destination. Contraindications to taking Losek are hepatic and renal types of insufficiency, pregnancy and lactation. Losek is produced in the form of a powder or tablets and is taken in a fairly high dose prescribed by a doctor, depending on the severity of the disease.

Rabeprazole

According to the results of clinical studies, the effectiveness of Rabeprazole is higher than that of Omeprazole in suppressing the symptoms of the disease. Rabeprazole also has a higher rate of impact on the source of the symptoms of the disease. Among the side effects of Rabeprazole are: dizziness, back pain, the occurrence of reactions allergic type, cough, rhinitis, drowsiness. Rabeprazole shows good results when used as monotherapy for duodenal and gastric ulcers. Another difference of Rabeprazole is the high bioavailability of the drug compared to Omeprazole at the first stages of treatment of gastrointestinal diseases.

Proton pump inhibitors (PPIs) occupy a leading position in a number of drugs for the treatment of diseases associated with high gastric acid production. Currently, this pharmacological group includes omeprazole, lansoprazole, pantoprazole, esomeprazole and rabeprazole. Some aspects of the discussion regarding the benefits of one or another PPI need to be covered and understood. Particularly acute are the disputes around omeprazole and pantoprazole, which are similar in their pharmacodynamic characteristics and clinical efficacy. Let us consider the discussed differences in the light of the available information on clinical pharmacology these drugs.

PPI mechanism of action

The mechanism of action of PPIs is to block H + /K + -ATPase, the enzyme responsible for the main step in the formation of hydrochloric acid (HCl). Irreversible (or long-term) blockade of the enzyme explains the long duration of the main pharmacodynamic effect of PPIs, which significantly exceeds the time spent by these drugs in the blood. PPIs are benzimidazole derivatives and are prodrugs, meaning they ideally form active form only in the secretory tubules of parietal cells, into the lumen of which sections of H + /K + -ATPase molecules protrude.

PPIs are unstable in an acidic environment, the probability of their penetration from the stomach cavity into the secretory tubules of parietal cells is negligible, especially compared to transport capabilities microvasculature mucous membrane of the stomach. For this reason, minimizing losses during the delivery of an inactive substance to the parietal cell leads to an increase in the effectiveness of these drugs. PPI protection from HCl is technically solved by using enteric dosage forms that release the active substance in the alkaline environment of the small intestine lumen.

The activation of PPI molecules proceeds with successive protonation of the pyridine and benzimidazole rings, and the addition of a hydrogen atom to the latter is possible only in the strongly acidic environment of the secretory tubules of parietal cells. When considering differences in the intensity of the main pharmacodynamic effect of various PPIs, attention is paid to the pKa values ​​of their pyridine and benzimidazole rings (pKa1 and pKa2, respectively) (Table 1). pKa is the dissociation constant, in this case it is determined by the pH values ​​at which half of the drug molecules are protonated: H + is added to the nitrogen atom of the pyridine (pKa1) and benzimidazole (pKa2) rings. Protonation processes also proceed at a low rate at pH > pKa, but when it decreases to the pKa level, half of the molecules are protonated, and at pH< pKa присоединение ионов водорода значительно ускоряется. рКа1 колеблется от 3,83 (лансопразол и пантопразол) до 4,53 (рабепразол). Омепразол и эзомепазол имеют рКа1 = 4,06. Таким образом, находясь в кишечном содержимом с рН = 5,5, в крови и цитозоле париетальной клетки с рН = 7,4, молекулы ИПП находятся в неионизированной форме, поэтому свободно проникают через биологические мембраны, в том числе через мембраны секреторных канальцев париетальных клеток. Оказавшись в просвете канальцев, ИПП подвергаются воздействию сильнокислой среды с рН, равным 1,2-1,3, и ионизируются (протонируются), теряя способность обратного прохождения через мембрану, то есть создается своеобразная «ловушка» для ИПП с повышением их концентрации в просвете канальцев в 1000 раз, по сравнению с концентрацией в крови и цитозоле париетальной клетки . Исходя из указанных значений видно, что среди ИПП быстрее накапливаются в секреторных канальцах париетальных клеток препараты с более высокими значениями рКа1. Если сравнить омепразол и пантопразол, то можно заметить, что пантопразол заметно медленнее концентрируется в просвете канальцев, чем омепразол.

The accumulation in the lumen of the secretory tubule of an ionized drug as a substrate accelerates the second stage of its activation. After a series of intramolecular changes, the nitrogen atom of the benzimidazole ring is protonated. pKa2 is significantly lower than pKa1 and ranges from 0.11 (pantoprazole) to 0.79 (omeprazole and esomeprazole). Lansoprazole and rabeprazole have pKa2 = 0.62. The higher the pKa2 value, the faster the nitrogen atom of the benzimidazole ring accepts a proton. Thus, omeprazole and esomeprazole are converted to their active form faster than pantoprazole, thereby being able to bind to the proton pumps faster.

As a result of two-step activation (some intermediate intramolecular rearrangements are not mentioned), tetracyclic sulfenamide and sulfenic acid derivatives are formed, capable of forming disulfide bonds with mercapto groups of cysteine ​​residues CYS813 and CYS822 of the proton pump with blockade of conformational transitions of the enzyme and release of water molecules.

The resumption of acid production occurs due to the synthesis of new molecules of the H + /K + -ATPase enzyme, the entry of “reserve” molecules contained in tubulovisicles and inaccessible to the action of drugs, and the breaking of disulfide bonds under the action of endogenous glutathione.

For pantoprazole, slower proton binding is said to be beneficial. With rapid activation, omeprazole binds CYS813, while with delayed activation, pantoprazole also binds CYS822 to form sulfonic acid. Omeprazole blocks CYS822 only to a small extent. The association of PPIs with CYS822 is resistant to the action of endogenous glutathione. However, any difference chemical properties We can consider a compound as an advantage of a drug only if it leads to an increase in the intensity of its main pharmacodynamic effect and an increase in the effectiveness of treatment with its use. And does a stronger bond of pantoprazole with H + /K + -ATPase matter, if it is known that for any modern PPI it is practically irreversible, and the restoration of acid production does not depend on its dissociation, but on the rate of incorporation of new proton pumps into the membrane of the secretory tubules parietal cells.

Pharmacokinetics

Differences in PPI pharmacokinetics are also being discussed today. So, for example, one of the most discussed differences between omeprazole and pantoprazole is the higher bioavailability of pantoprazole (77%), which does not change with course use, compared with omeprazole (35% with a single dose and 60% with a course application). It would be logical to assume that, in order to achieve a similar antisecretory effect, a PPI with greater bioavailability should be used at lower doses. But at the same time, most studies have proven comparable clinical efficacy of pantoprazole 40 mg with half the dose of omeprazole - 20 mg.

In addition, the maximum plasma concentration when taking omeprazole occurs after about 0.5-3.5 hours, when taking pantoprazole - after 2.0-3.0 hours, and when taking, for example, rabeprazole, the time to reach the maximum concentration ranges from 2 to 5 h. At the same time, higher values ​​of this parameter may contribute to a later delivery of the drug to the site of activation, and, conversely, more a short time The achievement of the maximum concentration in the blood plasma of omeprazole theoretically indicates its faster entry into the parietal cell.

The half-life of the drugs under consideration differs slightly: 0.6-1.5 hours for omeprazole and 0.9-1.2 hours for pantoprazole. Due to the ability to concentrate in the secretory tubules without reverse penetration into the vascular bed, the dependence of PPI pharmacodynamics on pharmacokinetics is weak, and the duration of their main pharmacodynamic effect significantly exceeds the average retention time of the drug in the blood.

However, the features of pharmacokinetics cannot be an independent argument in favor of any of the PPIs, as well as the color of its packaging. The advantages of one PPI over another, if any, can only be justified by the features of pharmacokinetics, if the latter are due to the optimization of its pharmacodynamics and clinical efficacy. Does pantoprazole demonstrate pharmacodynamic and clinical advantages over omeprazole when given at the same doses?

Pharmacodynamics of PPI

When comparing the intensity of the main pharmacodynamic effect of PPIs, it is better to talk about the same doses of drugs. Publications often compare the antisecretory effect of 20 mg of one PPI with 40 mg of another, which artificially creates the idea of ​​a drug used in a double dose as more pharmacodynamically effective. In this case, both pantoprazole and omeprazole can be used at a dose of 40 mg / day. In this regard, the results of a meta-analysis are interesting, which systematizes data on the average daily values ​​of gastric pH against the background of the use of various doses of PPIs in different categories of patients. And these data reliably demonstrate the lower antisecretory activity of pantoprazole compared to omeprazole: the calculated relative potential of the antisecretory effect, when compared with omeprazole (1.00), for pantoprazole is only 0.23.

Thus, pantoprazole, prescribed in equal doses with omeprazole, is a less active proton pump inhibitor, and its higher and more stable (same for single and course use) bioavailability is not an argument in the discussion about the benefits of this drug.

Clinical Efficiency

It is known that the rate of repair processes in the mucous membranes of the esophagus and stomach is pH-dependent. For the healing of the gastric epithelium in peptic ulcer disease, the proportion of time during which the pH exceeds 3 is considered important. Therapy of NSAID gastropathy and gastroesophageal reflux disease (GERD) requires gastric pH > 4 most of the day. Any PPI can provide these pH levels, and there are various national and international guidelines for their dosing and dose conversion when replacing. For example, the World Health Organization Center for Collaboration in Methodology of Statistical Research medicines(The WHO Collaborating Center for Drug Statistics Methodology) and the Canadian Gastroenterology Association consider doses of 20 mg/day of omeprazole and 40 mg/day of pantoprazole to be equivalent for the treatment of GERD (http://www.whocc.no/atcddd/).

Published data from many clinical studies that compared the effectiveness of different doses of omeprazole and pantoprazole in different categories of patients. So, in two blind, randomized studies, the same clinical efficacy of 20 mg / day of omeprazole and 40 mg / day of pantoprazole has been proven, according to the results of endoscopic healing of duodenal ulcers for 2, 4 and 8 weeks of therapy.

According to K. D. Bardhan et al. (1999), the use of omeprazole 20 mg / day and pantoprazole 40 mg / day does not show statistically significant differences in the level of healing in grade I esophagitis (according to the Savary-Miller classification). After 2 weeks of therapy with pantoprazole and omeprazole, the symptoms of GERD disappeared in 70% and 77%, respectively, after 4 weeks - in 79% and 84%, respectively. After 4 weeks, in the groups of patients treated with pantoprazole and omeprazole, erosions were epithelialized, respectively, in 84% and 89% of cases, after 8 weeks, in 90% and 95%, respectively.

According to a multicenter, double-blind, comparative study conducted in France, omeprazole 20 mg/day and pantoprazole 40 mg/day are equally effective in the treatment of grade II and III reflux esophagitis (according to the Savary-Miller classification): according to endoscopy conducted before and after 8 weeks of treatment, healing of the erosions occurred in 93% of patients treated with pantoprazole and 90% of patients treated with omeprazole.

Criteria for inclusion in the meta-analysis of J. J. Caro et al. (2001) epithelialization of erosions of the esophagus or its absence was observed during treatment with omeprazole (20 mg/day) and pantoprazole (40 mg/day) for 8 weeks. No differences were found in the level of healing.

The equivalence of 40 mg/day of omeprazole and pantoprazole in the treatment of grade II-III reflux esophagitis (according to Savary-Miller) was demonstrated in a randomized, double-blind, parallel group, multicenter study conducted in Austria, Germany, Portugal, Switzerland and the Netherlands. After 4 weeks, the proportion of patients with healed erosions when using omeprazole was 74.7%, and when using pantoprazole 77.4%.

Thus, the published data of randomized trials prove the same clinical efficacy of omeprazole, prescribed at 20 mg / day, and pantoprazole, prescribed at 40 mg / day, in the treatment of peptic ulcer, grade I reflux esophagitis and in 8-week therapy of II reflux esophagitis. and III degree (according to Savary-Miller).

Metabolism, drug interactions

It is known that proton pump inhibitors are biotransformed mainly by CYP2C19 and CYP3A4. Rabeprazole is metabolized to a greater extent by non-enzymatic mechanisms. However, it is known that for some isoenzymes of the cytochrome P-450 system, as well as for a number of transport enzymes, H + /K + -ATPase blockers are inhibitors, which has essential for our idea of drug interactions with the participation of drugs of this pharmacological group(Table 2).

Thus, an in vitro study showed that pantoprazole, to a greater extent than omeprazole, inhibits CYP2C9 (Ki, respectively, 6.5 ± 1.0 and 16.4 ± 3.0 μM) and CYP3A4 (Ki, respectively, 21, 9 ± 2.7 and 41.9 ± 5.9 µM). The lower the value of the inhibition constant (Ki), the higher the inhibitory activity of the drug in relation to the corresponding isoenzyme. Substrates of CYP2C9 are phenytoin, S-warfarin, tolbutamide, losartan, non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, piroxicam), irbesartan, carvedilol, etc. . CYP3A4 is the predominant isoenzyme of cytochrome P450 c the largest number substrates, which are amiodarone, amlodipine, atorvastatin, buspirone, verapamil, vincristine, hydrocortisone, dexamethasone, diazepam, disopyramide, itraconazole, carbamazepine, ketoconazole, clarithromycin, lovastatin, losartan, progesterone, propafenone, rifampicin, salmeterol, simvastatin, fentanazol, quinidine, cyclosporine, cimetidine, erythromycin, etc. Glibenclamide, amitriptyline, imipramine are both CYP2C9 and CYP3A4 substrates.

Data on drug interactions between proton pump inhibitors and substrate preparations of certain cytochrome P450 isoenzymes are contradictory: they contain opposite conclusions, references to rather old publications and databases that have not been updated for a long time. The results of in vivo and in vitro studies differ. Summarizing information about drug interactions of drugs, including proton pump inhibitors, is contained, for example, in the online pharmaceutical encyclopedia www.drugs.com (USA).

The most frequently discussed aspects of the interaction of PPIs with clopidogrel are discussed today. Clopidogrel is a prodrug. Its active metabolites are formed mainly by CYP2C19, but also by CYP1A2, CYP2B6 and CYP2C9. Proton pump inhibitors are often given in conjunction with clopidogrel to prevent mucosal damage and gastrointestinal bleeding. However, it has been shown that all PPIs are, to a greater or lesser extent, inhibitors of CYP2C19 and slow down the metabolic activation of clopidogrel, worsening its antiplatelet properties (Table 3).

The lower the Ki value of PPI, the higher its inhibitory activity against CYP2C19. However, an analysis of data from published studies indicates that the frequency of cardiovascular events against the background of clopidogrel does not increase due to the combined use with proton pump inhibitors.

Today, although the discussion regarding interactions of PPIs with clopidogrel continues, guidelines from the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA, USFDA) recommend avoiding the use of PPIs, unless clear there are no indications, and if necessary, use pantoprazole, which is a weak inhibitor of CYP2C19.

Many cytochrome P450 isoenzymes are involved in the metabolism of benzodiazepines. For example, biotransformation of diazepam is carried out using CYP3A4, CYP2C19, CYP3A5, CYP2B6, CYPCYP2C8, CYP2C9. Modern data are not enough for a comparative assessment of the interaction potential of omeprazole and pantoprazole with representatives of this pharmacological group.

The pathways of biotransformation of the dextrorotatory and levorotatory isomers of warfarin are different. The S-enantiomer, which is 5 times more active than R-warfarin, is metabolized mainly by CYP2C9, while the R-enantiomer is metabolized by CYP2C9, CYP1A2, CYP2C19, CYP3A4. Proton pump inhibitors can alter the activity of CYP2C19 and CYP3A4, but the significance of this factor for the interaction of warfarin with omeprazole or pantoprazole still needs to be analyzed.

Thus, today, based on updated data on drug interactions, we can talk about the advantage of pantoprazole over omeprazole only when they are used together with clopidogrel or citalopram.

Adverse drug reactions

Based on published data on the safety of proton pump inhibitors, an analysis was made by type and prevalence of adverse drug reactions (ADRs). For omeprazole and pantoprazole named as the same ADRs (dizziness, headache, asthenia, skin rash, abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting, cough, cervical fracture femur, rhabdomyolysis), and occurring only in one of the drugs (although the association with the use of only one of the compared PPIs has not been proven). With the use of omeprazole, hepatotoxicity, pancreatitis, interstitial nephritis, fever are described (the frequency of NLR is not specified), with the use of pantoprazole - Stevens-Johnson syndrome, Lyell's syndrome, thrombocytopenia (the frequency of NLR is not specified); with a frequency of more than 1%, gastroenteritis, urinary tract infections, arthralgia, back pain, dyspnea, infections of the upper respiratory tract, flu-like syndrome.

Conclusion

Omeprazole is an effective and relatively safe drug for the treatment of diseases associated with a high intensity of gastric acid production.

Pantoprazole is a proton pump inhibitor that, compared with omeprazole, has greater bioavailability, but less antisecretory activity and clinical efficacy in the treatment of peptic ulcer, grade I reflux esophagitis and in 8-week therapy of grade II and III reflux esophagitis according to Savary-Miller (equivalent to daily doses of 20 mg of omeprazole and 40 mg of pantoprazole).

Of the two proton pump inhibitors, pantoprazole can definitely be recommended only if co-administration with clopidogrel or citalopram is required.

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S. Yu. Serebrov,doctor of medical sciences, professor

GBOU VPO First Moscow State Medical University. I. M. Sechenov Ministry of Health of the Russian Federation, Moscow