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Inhibiteurs de la pompe à protons: la nouvelle génération

New generation proton pump inhibitors

  • Published:
Acta Endoscopica

Résumé

De nos jours, les patients en prise avec une pathologie d’intensité moyenne à forte en rapport avec l’hyperacidité sont traités de façon préférentielle à l’aide d’inhibiteurs de la pompe à protons (IPP). Il existe un large consensus à ce sujet. Même si les différentes substances disponibles sont toutes regroupées sous l’appellation d’IPP, il existe incontestablement des différences entre elles sur le plan de la pharmacocinétique, de la pharmacodynamique et de l’efficacité clinique. Les nouvelles molécules de seconde génération, représentées par la rabéprazole et l’ésoméprazole, possèdent de réels avantages par rapport à leurs prédécesseurs (omé-, lanso- et pantoprazole), en particulier dans le traitement de la maladie du reflux gastro-œsophagien (RGO). D’emblée, on remarque une inhibition plus rapide et plus prononcée de la sécrétion acide et un meilleur contrôle des symptômes. Comparé à tous les autres IPP (pKa=4), le rabéprazole (pKa=5) constitue une base puis puissante, Par conséquent, au niveau de la cellule pariétale, on assiste à une accumulation et une transformation plus rapides vers la forme active et, dès lors, une suppression de l’acidité plus précoce. De plus, par rapport à l’ésoméprazole, le rabéprazole est bien moins métabolisé par la voie des cytochromes hépatiques (CYP 2C19 et CYP3A4) et suit davantage la voie de la métabolisation non enzymatique. particularité fait que le rabéprazole, en comparaison avec l’ésoméprazole, est moins sensible aux interactions avec d’autres médications métabolisées par le biais des CYP 2C19 et CYP3A4. Contrairement à l’ésoméprazole, et jusqu’à présent, on n’a pas relaté pour le rebéprazole d’interactions médicamenteuses en relation avec les CYP450.

Summary

Patients who have to cope with moderate to severe acid-related diseases are now preferably treated with a proton pump inhibitor (PPI). There is a broad consensus about this. The various agents available all fit under the common heading of PPIs but pharmacokinetically, pharmacodynamically and as far as clinical efficacy is concerned there are indeed differences between them. The newer agents, of the second generation, represented by rabeprazole and esomeprazole, have clear advantages over their predecessors (omeprazole, lansoprazole and pantoprazole), particularly in the treatment of gastroesophageal reflux disease (GERD). In particular, the onset and degree of acid inhibition and symptom control is more rapid and greater. Compared with all other PPIs (pKa=4), however, rabeprazole (pKa=5) is a stronger base. The result of this is a more rapid concentration in the parietal cell, more rapid conversion into the active form and therefore more rapid acid inhibition. In addition to this, rabeprazole is metabolised to a far lesser extent than esomeprazole in the liver via the cytochrome pathway (CYP 2C19 and CYP3A4). A larger proportion is broken down non-enzymatically. This property means that rabeprazole is less susceptible than esomeprazole to interactions with other drugs metabolised via CYP 2C19 and CYP3A4. Unlike with esomeprázole, no CYP450-related drug interactions are know for rabeprazole to date.

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Références

  1. CHIBA N., DE GARA C.J., WILKINSON, HUNT R.H. — Speed of healing and symptom relief in grade II–IV oesophageal reflux disease: a meta-analysis.Gastroenterology, 1987,112, 1798–1810.

    Article  Google Scholar 

  2. TYTGAT G.N.J. — Shortcomings of the first generation proton-pump inhibitors.Eur. J. Gastroenterology, 2001,112, 1798–1810.

    Google Scholar 

  3. SACHS G.et al. —Ann. Rev. Pharmacol. Toxicol., 1995,35, 277.

    Article  CAS  Google Scholar 

  4. PANTOFLICKOVA D., DORA G., JORNOD P., RAVIC M., BLUM A.L. — Identification of the characteristics influencing the degree of antisecretory activity of PPI’s.Gastroenterology, 2000,118 (4), 5895 (Abstract).

    Google Scholar 

  5. BESANÇON M., SIMON A., SACHS, G.et al. — Sites of the gastric H,K-ATPase with extracytoplasmic thiol reagents.J. Biol. Chem., 1997,272, 22438–22446.

    Article  PubMed  Google Scholar 

  6. GARDNER J.D.et al. — Rabeprazole versus omeprazole: onset, duration and magnitude of gastric antisecretory effects.Gut, 2000,47 (Suppl. 3), A61.

    Google Scholar 

  7. ROBINSON M., MATON P.H., RODRIGUEZ S., GREENWOOD B., HUMPHRIES T.J. — Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease.Aliment. Pharmacol. Ther., 1997,11, 973–980.

    Article  PubMed  CAS  Google Scholar 

  8. LIND T.et al. — Esomeprazole provides improved acid controlversus omeprazole in patients with symptoms of gastro-oesophageal reflux disease.Aliment. Pharmacol. Ther., 2000,14, 861–867.

    Article  PubMed  CAS  Google Scholar 

  9. THOMSON A.B.R.et al. — Esomeprazole 40 mg provides more effective acid control than lansoprazole 30 mg during single and repeated administration.Gut, 2000,47 (Suppl. 3), A63

    Google Scholar 

  10. WILDER-SMITH C.et al. — Esomeprazole 40 mg provides more effective acid control than pantoprazole 40 mg.Gastroenterol., 2000,118, A22-A23.

    Article  Google Scholar 

  11. RÖHSS K.et al. — Esomeprazole 40 mg provides more effective acid control than rabeprazole 20 mg following single and repeated oral administration in patients with GERD symptoms.Scand. J. Gastroenterol., 2001,36 (Suppl. 233), 38.

    Google Scholar 

  12. BAISLEY K.et al. — Comparison of rabeprazole 10 mg with esomeprazole 20 mg in the control of gastric pH in healthy volunteers.Am. J. Gastroenterol., 2001,96 (Suppl. 9), Ps79.

    Google Scholar 

  13. BAISLEY K.et al. — Rabeprazole 20 mg compared with esomeprazole 40 mg in the control of intragastric pH in healthy volunteers.J. Gastroenterol. Hepatol., 2002,17 (Suppl.), A845.

    Google Scholar 

  14. ROBINSON M.et al. — Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive eosophagitis.Aliment. Pharmacol. Ther., 2002,16, 445–454.

    Article  PubMed  CAS  Google Scholar 

  15. RICHTER J.E., KAHRILAS P.J., JOHANSON J., MATON P., BREITER J.R., HWANG C.et al. — Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial.Am. J. Gastroenterol., 2001,96, 656–665.

    Article  PubMed  CAS  Google Scholar 

  16. KAHRILAS P., FALK G.W., JOHNSON D.A., SCHMITT C., COLLINS D.W., WHIPPLE J.et al. — Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial.Aliment. Pharmacol. Ther., 2000,14, 1249–1258.

    Article  PubMed  CAS  Google Scholar 

  17. KAHRILAS P.J.et al. — Efficacy of rabeprazole in endoscopy negative GERD patients with frequent moderate to severe heartburn symptoms.Gastroenterol., 2002,122 (Suppl.), A197–198.

    Google Scholar 

  18. KATZ P.O.et al. — Comparison of the new PPI esomeprazole, the S-isomer of omeprazole, vs. placebo for the treatment of symptomatic GERD.J. Gastroenterol., 2000,95, 2424–2425.

    Google Scholar 

  19. DEKKERS C.P.M., BEKER J.A., THJODLEIFSSON B.et al. — Double-blind placebo-controlled comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease.Aliment. Pharmacol. Ther., 1999,13, 49–57.

    Article  PubMed  CAS  Google Scholar 

  20. DELCHIER J.C., COHEN G., HUMPHRIES T.J. — Rabeprazole, 20 mg once daily or 10 mg twice daily, is equivalent to omeprazole, 20 mg once daily, in the healing of erosive gastro-oesophageal reflux disease.Scand. J. Gastroenterol., 2000,35, 1245–1250.

    Article  PubMed  CAS  Google Scholar 

  21. THIODLEIFSSON B., BEKER J.A., DEKKERS C.et al. — Rabeprazolevs. omeprazole in preventing relapse of erosive or ulcerative gastroesophageal reflux disease: a double-blind. multicenter, European trial. The European Rabeprazole Study Group.Dig. Dis. Sc., 2000,45, 845–853.

    Article  Google Scholar 

  22. JOHNSON D.A.et al. — Esomeprazole once daily for 6 months in effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety.Am. J. Gastroenterol., 2001,96, 27–34.

    Article  PubMed  CAS  Google Scholar 

  23. HUMPHRIES T.et al. —Am. J. Gastroenterol., 1999,94, A2587.

    Google Scholar 

  24. ISHIZAKI T., JORAI Y. — Review article: cytochrome P450 and the metabolism of proton pump inhibitors-emphasis on rabeprazole.Aliment. Pharmacol. Ther., 1999,13 (Suppl. 3), 27–36.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Gastro-entérologue, Médecin des Hôpitaux de l’Assistance Publique de Paris, (France)

    C. Florent

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  1. C. Florent
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Florent, C. Inhibiteurs de la pompe à protons: la nouvelle génération. Acta Endosc 32 (Suppl 1), 445–453 (2002). https://doi.org/10.1007/BF03020578

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  • DOI: https://doi.org/10.1007/BF03020578

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