Comparative pharmacology: omeprazole vs pantoprazole

Proton pump inhibitors (PPIs) are one of the most popular drugs, without which treatment of peptic ulcers and other diseases of the digestive tract associated with increased formation of hydrochloric acid is essential. This group includes only a few drugs that have the same mechanism of action, similar indications and side effects. But are their properties completely comparable? We decided to take a closer look at two proton pump inhibitors, which are the drugs of choice for the treatment of most common stomach diseases: omeprazole and pantoprazole.

general information

Omeprazole is the first PPI, synthesized back in 1978 and entering clinical practice 10 years later. 40 years later, it became one of the best-selling drugs in the world: in the United States alone, 58 million prescriptions for this drug were issued in 2022. The actual sales volumes of the drug are much higher, since one of its forms belongs to the OTC group, both in the Russian Federation and in many other countries of the world [1].

Pantoprazole appeared a little later than its predecessor: its research began in 1985, and in 1994 the drug was already registered in Germany. In 2022, there were approximately 29 million prescriptions written for pantoprazole in the United States [1].

Drug analogues

If we compare these drugs and analogues, the latter include other components from the group of proton pump inhibitors and are an order of magnitude higher:

None of these medications should be taken uncontrolled without examination. They can mask the symptoms of malignant stomach diseases, so it is important to first visit a doctor and undergo the necessary procedures.

Mechanism of action

Both omeprazole and pantoprazole are benzimidazole derivatives, which results in similar physicochemical properties and pharmacological actions. Both drugs are prodrugs: they form the active form in the secretory tubules of parietal cells. It is into the lumen of the latter that parts of the molecules of the enzyme responsible for the main stage of the production of hydrochloric acid—H+/K+-ATPase—protrude.

Activation of omeprazole and pantoprazole occurs with the sequential addition of a hydrogen atom to the pyridine and benzimidazole rings. The main condition for activation is a strongly acidic environment, corresponding to that in the secretory tubules of parietal cells.

After ionization, omeprazole and pantoprazole can no longer penetrate the cell membrane and accumulate inside the tubules. The concentration of drugs in the lumen of the secretory tubules is 1000 times higher than the concentration in the blood and in the parietal cell. It is noteworthy that pantoprazole concentrates in the tubular lumen more slowly than omeprazole: the time required for 50% blockade of H+/K+ ATPase by omeprazole and pantoprazole is 400 and 1100 seconds, respectively. Thus, omeprazole is activated faster than pantoprazole and binds to the proton pump in a shorter time [2, 3].

The results of an in vitro study showed that omeprazole achieved maximum proton pump inhibition after 20 minutes of administration, and pantoprazole after 30 minutes.

Why is heartburn dangerous?

Many people neglect heartburn and make a mistake, especially if the burning sensation bothers you often. The danger of heartburn is not only that it may hide the diseases described above, which require proper diagnosis and treatment. The upward release of gastric juice itself greatly irritates the esophageal mucosa, contributing to the appearance of inflammation. This is fraught with the development of diseases such as esophagitis, erosions and peptic ulcers. Long-term chronic inflammation of the esophagus leads to a precancerous condition known as Barrett's esophagus.

Pharmacokinetic and pharmacodynamic properties

Omeprazole and pantoprazole differ from each other in at least two pharmacokinetic parameters.

Bioavailability

Omeprazole is 35% with a single dose and 60% when taken as a course, while the bioavailability of pantoprazole at a course dose reaches 77%. It should be noted that, despite the significant difference in the bioavailability of the drugs, their clinical effectiveness in equal doses is not comparable. According to research results, the acid-blocking effect of 20 mg of omeprazole is comparable to the effectiveness of pantoprazole at a dose of 40 mg [4].

Time to reach maximum concentration

in blood plasma for omeprazole is 0.5–3.5 hours. Pantoprazole reaches maximum concentration 2–3 hours after administration. Obviously, the difference between the upper and lower limits for achieving this indicator does not allow us to correctly compare drugs and draw a definite conclusion.

Top 7. Emanera

Rating (2021): 4.40

Best price Among Omeprazole substitutes, this drug has the most affordable price. The new generation medicine costs a little more than 200 rubles.

• Characteristics

  Average price: 209 rub.

  Read also:  Remantadine tab. 50 mg per circuit. cell pack No. 10x2 (rimantadine)
• Country: Slovenia
• Manufacturer: KRKA
• Active ingredient: esomeprazole

The modern new generation Omeprazole substitute is also a proton pump inhibitor, but has higher bioavailability. Therefore, the effect of treatment is achieved much faster. "Emanera" already at the beginning of the course relieves the symptoms of stomach diseases. Taking courses reliably protects against relapses. Among all drugs based on esomerpazole, many doctors prefer the pharmacological version, which is an order of magnitude more effective than the cheap Omeprazole, but at the same time it also has a more than affordable price. This is the best option for those who are looking for a modern substitute for an outdated product without harming their wallet. The drug has virtually no side effects, but requires gradual withdrawal to avoid relapses.

Advantages and disadvantages

• Brings relief quickly
• Optimal price-performance ratio
• Does not give side effects
• New generation drug

• Requires gradual withdrawal
• Not sold in all pharmacies

Efficiency

Over the past decades, a number of studies have been conducted that examined the comparative effectiveness of different doses of omeprazole and pantoprazole in different categories of patients.

• Two blinded randomized studies confirmed comparable clinical efficacy of omeprazole 20 mg per day and pantoprazole 40 mg per day for duodenal ulcers over 2, 4 and 8 weeks of treatment [5, 6].
• The results of a multicenter, double-blind study showed comparable effectiveness of omeprazole 20 mg per day and pantoprazole 40 mg per day for reflux esophagitis after 8 weeks of therapy [7].
• According to the results of a meta-analysis, when treating with omeprazole 20 mg per day and pantoprazole 40 mg per day, the effectiveness of healing of esophageal erosions after 8 weeks of therapy was comparable [8].

Thus, the research results demonstrate a comparable clinical effect of omeprazole at a dosage of 20 mg per day and pantoprazole at a dose of 40 mg per day for peptic ulcers and reflux esophagitis.

What do the experts say?

Both products are generics of the drug Losek, which was released back in 1989 in Sweden. Thus, they are created on the basis of the original product, but they differ in purification, the composition of additional substances, and they want to completely replace it in terms of the main component.

According to gastroenterologist Natalya Antipova, it cannot be said that Omez is more effective than Omeprazole in terms of therapeutic effects.

Both remedies work at the same speed, have a prolonged effect, and are excellent for gastritis and other hypersecretory diseases.

The difference is great in the degree of purification, the quality of production of the main component, and the set of additional substances, therefore Omez has a lower risk of side effects.

If we compare the severity of unpleasant effects, even with the same list of cheaper products, they are more serious. Thus, nausea occurs when taking Omez much less frequently than when treating with Omeprozole. Moreover, there is Omez-DSR, which contains domperidone, an antiemetic component. It can be taken if the patient has such reactions. The list of auxiliary components of the Indian product is more precise; they are more expensive, which affects the price. But the danger of developing negative actions from the product is minimized as much as possible.

Drug-drug interactions

PPIs undergo biotransformation in the liver with the help of isoenzymes of the cytochrome P450 system, primarily CYP2C9 and CYP3A4. At the same time, H+/K+-ATPase blockers inhibit cytochrome P-450 isoenzymes, which is of great importance in terms of drug interactions. The difference in the severity of inhibition of different isoenzymes determines the ability of PPIs to interact with drugs that are substrates for the corresponding enzymes [4].

Studies show that pantoprazole blocks both CYP2C9 and CYP3A4 more strongly than omeprazole. Consequently, the possibility of drug interactions of the former with respect to drugs that are substrates for the corresponding enzyme is higher compared to the latter.

• Substrates for CYP2C9: warfarin, losartan, non-steroidal anti-inflammatory drugs, including ibuprofen and diclofenac, irbesartan, carvedilol [9–11].
• Substrates for CYP3A4: amiodarone, amlodipine, buspirone, verapamil, carbamazepine, itraconazole, ketoconazole, clarithromycin, lovastatin, progesterone, fluconazole, erythromycin and others.
• The substrates for both forms are glibenclamide, amitriptyline and imipramine.

Data on the inhibitory activity of omeprazole and pantoprazole suggest that omeprazole has a minimal risk of drug-drug interaction with NSAIDs [11]. Let us remember that the latter are often combined with PPIs to reduce the risk of gastropathy.

The ability to enter into drug interactions with clopidogrel is also important. It is known that PPIs can be prescribed in combination with this antiplatelet agent to prevent damage to the mucous membrane of the digestive tract and the development of gastrointestinal bleeding. Clopidogrel is a prodrug whose active metabolites are formed by a number of cytochrome P450 isoenzymes. All PPIs, being inhibitors of isoenzymes of the cytochrome system, interact with clopidogrel, slowing down its activation and reducing its antiplatelet ability [12, 13].

A special role is played by the ability of PPIs to inhibit the enzyme CYP2C19, the main isoenzyme involved in the activation of clopidogrel. Omeprazole is a more potent inhibitor of CYP2C19: its ability to inhibit this isoenzyme is several times higher than pantoprazole. Thus, pantoprazole has an advantage when combined with clopidogrel compared to omeprazole [4].

A similar situation occurs when pantoprazole or omeprazole is taken together with the antidepressant citalopram [4].

Adverse reactions

Both PPIs, omeprazole and pantoprazole, have a number of identical side effects. Thus, when taking them, dizziness, headache, urticaria, abdominal pain, constipation or diarrhea, flatulence, and other dyspeptic symptoms, in particular nausea and vomiting, may develop. Rare adverse events associated with both drugs include hip fracture and rhabdomyolysis [4].

Along with general side effects, omeprazole and pantoprazole also exhibit individual side effects. Thus, with the use of omeprazole, damage to the liver, kidneys, pancreatitis, and fever may develop. In patients receiving pantoprazole, life-threatening complications were recorded - Stevens-Johnson syndrome (severe hypersensitivity reaction with damage to the skin and mucous membranes), Lyell's syndrome (a very severe form of allergic bullous dermatitis), as well as changes in the blood picture - thrombocytopenia. With a probability of more than 1%, when using pantoprazole, acute gastroenteritis, pain in the joints, back, as well as dyspnea, upper respiratory and genitourinary tract infections, and a flu-like condition may occur [4].

Top 4. Losek MAPS

Rating (2021): 4.49

The original omeprazole drug Losec MAPS belongs to the first generation of PPIs, but in quality and effectiveness it is many times superior to the Russian Omeprazole. This is an original drug, often prescribed by doctors.

• Characteristics

  Average price: 412 rub.

• Country: Sweden
• Manufacturer: AstraZeneca AB
• Active ingredient: omeprazole

The original “brand” drug omeprazole, despite the emergence of new generation tablets, still remains the gold standard of antisecretory therapy. This he owes to safety and proven effectiveness. Russian "Omeprazole" is a generic and is significantly inferior to the original drug in terms of therapeutic effect. This is noted by both doctors and patients. Losec MAPS is the best medicine based on omeprazole. Sustained improvement is observed after a short course of use. Long-term therapy reduces the relapse rate. The high quality of the drug minimizes the severity of side effects. And its safety allows it to be prescribed to pregnant women to relieve heartburn. Doctors say the only significant drawback is the high cost of the drug, due to which many patients abandon the original drug in favor of a cheap Russian generic.

Advantages and disadvantages

• Original high quality product
• Fast therapeutic effect
• No side effects
• Positive reviews from doctors

• High price

Conclusion

Omeprazole and pantoprazole have comparable antisecretory activity (at doses of 20 mg per day and 40 mg per day, respectively) and safety profile. The main differences between the drugs are their ability to inhibit isoenzymes of the cytochrome P450 system and the associated drug-drug interactions. For patients who need to take a PPI in combination with clopidogrill and citalopral, it is more advisable to opt for pantoprazole, as a drug with lower inhibitory activity against the isoenzyme involved in the activation of the corresponding antiplatelet or antidepressant.

Sources

1. The Top 300 of 2022. Provided by the ClinCalc DrugStats Database. URL: https://clincalc.com/DrugStats/Top300Drugs.aspx (accessed 07/24/2021).
2. Kusano M., Kuribayashi S., Kawamura O., Shimoyama Y. et al. A Review of the Management of Gastric Acid-Related Diseases: Focus on Rabeprazole. Clinical Medicine Insights // Gastroenterology. 2011: 3, 31–343.
3. Roche VF The Chemically Elegant Proton Pump Inhibitors // American Journal of Pharmaceutical Education. 2006; 70(5), Article 101:1–11.
4. Maev I.V., Oganesyan T.S., Kucheryavyi Yu.A. Comparative effectiveness of triple first-line anti-helicobacter therapy using pantoprazole and omeprazole // Attending physician, 2010. T. 2. P. 2-7.
5. De Francesco V., Margiotta M., Zullo A. et al. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori // Ann. Intern. Med. 2006; 144:94–100.
6. Kudryavtseva L.V., Isakov V.A.. Ivannikov I.O. et al. Resistance of Helicobacter pylori to metronidazole, clarithromycin and amoxicillin in Moscow, St. Petersburg and Abakan in 2001 // Pediatrics, 2002. No. 2 ( Application). pp. 61–63.
7. Sjostedt S., Sagar M., Lindberg G. et al. Prolonged and profound acid inhibition is crucial in Helicobacter pylori treatment with a proton pump inhibitor combined with amoxicillin // Scand. J. Gastroenterol. 1998; 33: 39–43.
8. Sachs G. Synthesis or rupture: duration of acid inhibition by proton pump inhibitors // Drugs Today. 2003. Vol. 39 (Suppl. A). R. 11–14.
9. Lapina O. D. Mechanism of action of proton pump inhibitors // Ros. magazine gastroenterol., hepatol., coloproctol., 2002. No. 2. P. 38–44.
10. Pan WJ et al. Lack of a pharmacokinetic interaction between lansoprazole or pantoprazole and theophylline // Aliment. Pharmacol. Ther. 2000; 14 (3): 345–52.
11. Blume H., Donath F., Warnke A., Schug BS Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors // Drug Safety. 2006; 29(9):769–784.
12. Juurlink DN, Gomes T, Ko DT et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel // CMAJ. 2009; 180: 713–718.
13. Bliesath H. et al. Pantoprazole does not interact with nifedipine in man under steady-state conditions // Int. J. Clin. Pharmacol. Ther. 1996. Vol. 34 (1 Suppl.). S81–85.