The choice of proton pump inhibitor from the standpoint of efficacy and safety in a particular patient

Proton pump inhibitors are a diverse class of drugs with unique acid suppression properties. The aim of the work was to present the therapeutic benefits of rabeprazole and pantoprazole in clinical practice. Numerous studies have demonstrated the high effectiveness of proton pump inhibitors and the relative safety of taking these drugs. However, it is necessary to increase the awareness of doctors and pharmacists regarding the possibility of complications during treatment with proton pump inhibitors in a polymorbid patient. The choice of proton pump inhibitors should be based on the clinical situation, concomitant pathology and therapy, the presence of risk factors in the patient, the speed and stability of the effect of the drug. Rabeprazole is converted from prodrug to drug faster than other drugs, and thus creates a greater gradient of prodrug concentration on the membrane secretory tubules. The pharmacodynamics of rabeprazole does not depend on gene polymorphism; in this regard, there is no need for dose adjustment in fast metabolizers. In addition, a distinctive feature of rabeprazole is the ability to more stimulate the production of mucin, thereby providing an additional cytoprotective effect.

A feature of the metabolism of pantoprazole is that in addition to binding to cysteine 813, there is an additional connection with cysteine 822, which ensures the restoration of acid secretion only the synthesis of a new protein and, as a result, the longest lasting effect of the drug. High pH selectivity characterizes the low probability of inhibition of proton pumps in tissues with a less acidic pH, i.e. determines the specificity of action only in the parietal cells of the stomach and the greatest safety of long-term use in patients with comorbid pathology. Among all proton pump inhibitors, pantoprazole and rabeprazole have the lowest affinity for the cytochrome P450 system and lower inhibitory activity against CYP2C19, demonstrating a minimal risk of drug interactions. 

1. Lapina T. L. Farmakologicheskie osnovy antisekretornoi terapii [Pharmacological basis of antisecretory therapy] // Russkii meditsinskii zhurnal. Bolezni organov pischevareniya. 2005. No. 1. S. 23. https://www.rmj.ru/articles/bolezni_organov_pishchevareniya/Farmakologicheskie_osnovy_antisekretornoy_terapii/#ixzz6AQH1cAoo.

2. Burget D. W., Chiverton K. D., Hunt R. H. Is there an optimal degree of acid supression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression // Gastroenterology. 1990; 99: 345–351.

3. Scally B., Emberson J. R., Spata E., et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomized trials // Lancet Gastroenterol Hepatol. 2018; 3 (4): 231–241.

4. Lanas A., Chan F. K. L. Peptic ulcer disease // Lancet. 2017; 390 (10094): 613–624. 5. Chan F. K. L., Lau J. Y. W. Peptic ulcer disease. In: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 10th ed. Philadelphia: Saunders Elsevier; 2015: chap 14.

5. Lopina T. L., Serebrova S. B. Osnovnye farmakokineticheskie kharakteristiki ingibitorov protonnogo nasosa I effektivnost ikh deistviya. Posobie dlya vrachei [The main pharmacokinetic characteristics of proton pump inhibitors and their effectiveness. A manual for doctors]. M., 2016. 44 s.

6. Peptic ulcer. Clinical recommendations of the Russian Gastroenterological Association and the Russian Society of Colorectal Surgeons, Russian Endoscopic Society, 2019. 41 p.

7. Shin J. M., Sachs G. Restoration of acid secretion following treatment with proton pump inhibitors // Gastroenterology. 2002; 123: 1588–1597.

8. Cundy T., Dissanayake A. Severe hypomagnesaemia in long-term users of protonpump inhibitors // Clin Endocrinol (Oxf). 2008; 69 (2): 338–341.

9. Lam J., Schneider J., Zhao W., Corley D. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency // JAMA. 2013; 310 (22): 2435–2442.

10. Ding J., Heller D. A., Ahern F. M., Brown T. V. The relationship between proton pump inhibitor adherence and fracture risk in the elderly // Calcif Tissue Int. 2014; 94 (6): 597–607.

11. Lombardo L., Foti M., Ruggia O., Chiecchio A. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy // Clin. Gastroenterol. Hepatol. 2010; 8 (6): 504–508.

12. Keszthelyi D., Jansen S. V., Schouten G. A., et al. Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case-control study // Aliment Pharmacol Ther. 2010; 32: 1124–1128. DOI: 10.1111/j.1365- 2036.2010.04453.x. [PubMed] [CrossRef] [Google Scholar].

13. Jalving M., Koornstra J. J., Wesseling J., Boezen H. M., de Jong S., Kleibeuker J. H. Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy // Aliment Pharmacol Ther. 2006; 24: 1341– 1348. DOI: 10.1111/j.1365-2036.2006.03127.x. [PubMed] [CrossRef]. [Google Scholar].

14. Ally M. R., Veerappan G. R., Maydonovitch C. L., et al. Chronic proton pump inhibitor therapy associated with increased development of fundic gland polyps // Dig Dis Sci. 2009; 54: 2617–2622. DOI: 10.1007/s10620-009-0993-z. [PubMed] [CrossRef] [Google Scholar].

15. Tran-Duy A., Spaetgens B., Hoes A. W., de Wit N. J., Stehouwer C. D. Use of proton pump inhibitors and risks of fundic gland polyps and gastric cancer: systematic review and meta-analysis // Clin Gastroenterol Hepatol. 2016; 14: 1706–1719. DOI: 10.1016/j.cgh.2016.05.018. [PubMed] [CrossRef] [Google Scholar].

16. Eslami L., Nasseri-Moghaddam S. Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions? // Arch Iran Med. 2013; 16 (8): 449–458.

17. Baker R. Acute tubulointerstitial nephritis: overview. Oxford Textbook of Clinical Nephrology (4 ed.). 2016. Section 4; Chapter 83: 669–677.

18. Geevasinga N., Coleman P. L., Webster A. C., Roger S. D. Proton pump inhibitors and acute interstitial nephritis // Clin Gastroenterol Hepatol. 2006; 4 (5): 597–604.

19. Shih C. J. et al. Proton pump inhibitor use represents an independent risk factor for myocardial infarction // Int J Cardiol. 2014; 177 (1): 292–297.

20. Brunner G. et al. Long-term, open-Label triaL: safety and efficacy of continuous maintenance treatment with pantoprazole for up to 15 years in severe acidpeptic disease // Aliment Pharmacol Ther. 2012.

21. Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC). 2009. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm (accessed Nov 1 2010)].

22. Interaction between clopidogrel and protonpump inhibitors. 2010. http://www.ema.europa.eu/humandocs/PDFs/EPAR/Plavix/17494810en.pdf (accessed June 15 2010).