The proton-pump inhibitors: Similarities and differences

  • John Horn
    Address correspondence to: John Horn, PharmD, Department of Pharmacy, University of Washington School of Pharmacy, Health Sciences Building, Room T-341, 1959 NE Pacific Street, Seattle, WA 98185.
    University of Washington School of Pharmacy, Seattle, Washington, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.



      This paper examines the clinical pharmacology of the proton-pump inhibitors (PPIs) and briefly reviews some comparative studies of these agents.


      PPIs have emerged as the treatment of choice for acidrelated diseases, including gastroesophageal reflux disease (GERD) and peptic ulcer disease. Although these drugs—omeprazole, lansoprazole, pantoprazole, and rabeprazole—share a common structure (all are substituted benzimidazoles) and mode of action (inhibition of H+,K+-adenosine triphosphatase [ATPase]), each differs somewhat in its clinical pharmacology.


      In comparative clinical trials found in MEDLINE®, PPIs administered once daily produced endoscopic evidence of healing in >90% of patients with duodenal ulcer after 4 weeks of treatment, in >90% of those with gastric ulcer after 6 weeks of treatment, and in >90% of those with ulcerative or erosive GERD after 8 weeks of treatment. Maintenance therapy with daily doses of a PPI has been shown to be an effective means of preventing GERD relapse. PPIs also inhibit the growth of Helicobacter pylori, now recognized as an important factor in peptic ulcer disease, and, when administered in combination with antibiotics, provide the best treatment for eradication of the bacterium. Rabeprazole has a more rapid onset of H+,K+-ATPase inhibition than the other PPIs and, compared with omeprazole, a greater effect on intragastric pH after the first dose. Omeprazole and lansoprazole have a greater potential for drugdrug interactions than do pantoprazole and rabeprazole.


      Although the individual PPIs have similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Sachs G
        Proton pump inhibitors and acid-related diseases.
        Pharmacotherapy. 1997; 17: 22-37
        • Sachs G
        • Shin JM
        • Briving C
        • et al.
        The pharmacology of the gastric acid pump: The H+,K+ ATPase.
        Annu Rev Pharmacol Toxicol. 1995; 35: 277-305
        • Fujisaki H
        • Shibata H
        • Oketani K
        • et al.
        Inhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione.
        Biochem Pharmacol. 1991; 42: 321-328
        • Williams MP
        • Pounder RE
        The pharmacology of rabeprazole.
        Aliment Pharmacol Ther. 1999; 13: 3-10
        • Besancon M
        • Simon A
        • Sachs G
        • Shin JM
        Sites of reaction of the gastric H,KATPase with extracytoplasmic thiol reagents.
        J Biol Chem. 1997; 272: 22,438-22,446
        • Huang JQ
        • Hunt RH
        pH, healing rate and symptom relief in acidrelated diseases.
        Yale J Biol Med. 1996; 69: 159-174
        • Goldberg HI
        • Dodds WJ
        • Gee S
        • et al.
        Role of acid and pepsin in acute experimental esophagitis.
        Gastroenterology. 1969; 56: 223-230
        • Williams MP
        • Sercombe J
        • Hamilton MI
        • Pounder RE
        A placebo-controlled trial to assess the effects of 8 days of dosing with rabeprazole versus omeprazole on 24-h intragastric acidity and plasma gastrin concentrations in young healthy male subjects.
        Aliment Pharmacol Ther. 1998; 12: 1079-1089
        • Fitton A
        • Wiseman L
        Pantoprazole. A review of its pharmacological properties and therapeutic use in acidrelated disorders.
        Drugs. 1996; 51: 460-482
        • Langtry HD
        • Wilde MI
        Lansoprazole: An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders.
        Drugs. 1997; 54: 473-500
        • Verdú EF
        • Armstrong D
        • Fraser R
        • et al.
        Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole.
        Gut. 1995; 36: 539-543
        • Koop H
        • Kuly S
        • Flüg M
        • et al.
        Intragastric pH and serum gastrin during administration of different doses of pantoprazole in healthy subjects.
        Eur J Gastroenterol Hepatol. 1996; 8: 915-918
        • Verdú EF
        • Armstrong D
        • Idström JP
        • et al.
        Effect of curing Helicobacter pylori infection on intragastric pH during treatment with omeprazole.
        Gut. 1995; 37: 743-748
        • Smout AJPM
        Is the sensitivity to gastric acid inhibition Helicobacter pylori status-dependent?.
        Scand J Gastroenterol. 1998; 33: 32-35
        • Bell NV
        • Burget D
        • Howden CW
        • et al.
        Appropriate acid suppression for the management of gastro-oesophageal reflux disease.
        Digestion. 1992; 51: 59-67
        • Robinson M
        • Maton PN
        • Rodriguez S
        • et al.
        Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease.
        Aliment Pharmacol Ther. 1997; 11: 973-980
        • Dekkers CPM
        • Beker JA
        • Thjodleifsson B
        • et al.
        Doubleblind 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
        • Mössner J
        • Hölscher AH
        • Herz R
        • Schneider A
        A doubleblind study of pantopra-zole and omeprazole in the treatment of reflux oesophagitis: A multicentre trial.
        Aliment Pharmacol Ther. 1995; 9: 321-326
        • Birbara C
        • Breiter J
        • Collins D
        • et al.
        Rabeprazole: Preventing endoscopic and symptomatic relapse in erosive or ulcerative GERD.
        Am J Gastroenterol. 1998; 93 (Abstract): 1630
        • Howden CW
        • Hunt RH
        The relationship between suppression of acidity and gastric ulcer healing rates.
        Aliment Pharmacol Ther. 1990; 4: 25-33
        • Richardson P
        • Hawkey CJ
        • Stack WA
        Proton pump inhibitors: Pharmacology and rationale for use in gastrointestinal disorders.
        Drugs. 1998; 56: 307-335
        • Dekkers CPM
        • Beker JA
        • Thjodleifsson B
        • et al.
        Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer: A European multicentre study.
        Aliment Pharmacol Ther. 1998; 12: 789-795
        • Burget DW
        • Chiverton SG
        • Hunt RH
        Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression.
        Gastroenterology. 1990; 99: 345-351
        • Humphries TJ
        • Spera A
        • Breiter J
        • et al.
        Rabeprazole sodium once daily is superior to ranitidine 150mg bid in the healing of active duodenal ulcer.
        Gastroenterology. 1997; 112 (Abstract): A154
        • Dekkers CPM
        • Beker JA
        • Thjodleifsson B
        • et al.
        Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: A European multicentre study.
        Aliment Pharmacol Ther. 1999; 13: 179-186
        • Hirschowitz BI
        Zollinger-Ellison syndrome: Pathogenesis, diagnosis, and management.
        Am J Gastroenterol. 1997; 92: 44S-50S
        • Qureshi W
        • Rashid S
        Zollinger-Ellison syndrome: Improved treatment options for this complex disorder.
        Postgrad Med. 1998; 104: 155-158
        • Qureshi W
        • Rashid S
        Zollinger-Ellison syndrome: Improved treatment options for this complex disorder.
        Postgrad Med. 1998; 104: 163-164
        • Maton PN
        Zollinger-Ellison syndrome: Recognition and management of acid hypersecretion.
        Drugs. 1996; 52: 33-44
        • Frucht H
        • Maton PN
        • Jensen RT
        Use of omeprazole in patients with Zollinger-Ellison syndrome.
        Dig Dis Sci. 1991; 36: 394-404
        • Hirschowitz BI
        • Mohnen J
        • Shaw S
        Long-term treatment with lansoprazole for patients with Zollinger-Ellison syndrome.
        Aliment Pharmacol Ther. 1996; 10: 507-522
        • Mignon M
        • Merrouche M
        • Gardner J
        • et al.
        Rabeprazole therapy effective in Zollinger-Ellison syndrome and idiopathic gastric acid hypersecretion.
        Gastroenterology. 1999; 116 (Abstract): A253
        • Cameron AJ
        Management of Barrett's esophagus.
        in: Mayo Clin Proc. 73. 1998: 457-461
        • Bremner CG
        • Bremner RM
        Barrett's esophagus.
        Surg Clin North Am. 1997; 77: 1115-1137
        • Peters FTM
        • Ganesh S
        • Kuipers EJ
        • et al.
        Endoscopic regression of Barrett's esophagus during omeprazole treatment: A randomized double blind study.
        Gut. 1999; 45: 489-494
        • Wilkinson SP
        • Biddlestone L
        • Gore S
        • Shepherd NA
        Regression of columnarlined (Barrett's) oesophagus with omeprazole 40 mg daily: Results of 5 years of continuous therapy.
        Aliment Pharmacol Ther. 1999; 13: 1205-1209
      1. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease Helicobacter pylori in peptic ulcer disease. JAMA. 272. 1994: 65-69
        • The European Helicobacter pylori Study Group^
        Current European concepts in the management of Helicobacter pylori infection: The Maastricht Consensus Report.
        Gut. 1997; 41: 8-13
        • Nakao M
        • Malfertheiner P
        Growth inhibitory and bactericidal activities of lansoprazole compared with those of omeprazole and pantoprazole against Helicobacterpylori.
        Helicobacter. 1998; 3: 21-27
        • Hirai M
        • Azuma T
        • Ito S
        • et al.
        A proton pump inhibitor, E3810, has antibacterial activity through binding to Helicobacter pylori.
        J Gastroenterol. 1995; 30: 461-464
        • Tsuchiya M
        • Imamura L
        • Park J-B
        • Kobashi K
        Helicobacter pylori urease inhibition by rabeprazole, a proton pump inhibitor.
        Biol Pharm Bull. 1995; 18: 1053-1056
        • McGowan CC
        • Cover TL
        • Blaser MJ
        The proton pump inhibitor omeprazole inhibits acid survival of Helicobacter pylori by a urease-independent mechanism.
        Gastroenterology. 1994; 107: 738-743
        • Mauch F
        • Bode G
        • Malfertheiner P
        Identification and characterization of an ATPase system of Helicobacter pylori and the effect of proton pump inhibitors.
        Am J Gastroenterol. 1993; 88 (Letter): 1801-1802
        • Stack WA
        • Knifton A
        • Thirlwell D
        • et al.
        Safety and efficacy of rabeprazole in combination with four antibiotic regimens for the eradication of Helicobacter pylori in patients with chronic gastritis with or without peptic ulceration.
        Am J Gastroenterol. 1998; 93: 1909-1913
        • Chu K-M
        • Choi H-K
        • Tuen HH
        • et al.
        A prospective randomized trial comparing the use of omeprazole-based dual and triple therapy for eradication of Helicobacter pylori.
        Am J Gastroenterol. 1998; 93: 1436-1442
        • Schwartz H
        • Krause R
        • Sahba B
        • et al.
        Triple versus dual therapy for eradicating Helicobacter pylori and preventing ulcer recurrence: A randomized, doubleblind, multicenter study of lansoprazole, clarithromycin, and/or amoxicillin in different dosing regimens.
        Am J Gastroenterol. 1998; 93: 584-590
        • Adamek RJ
        • Bethke TD
        • The International Pantoprazole HP Study Group
        Cure of Helicobacter pylori infection and healing of duodenal ulcer: Comparison of pantoprazolebased oneweek modified triple therapy versus two-week dual therapy.
        Am J Gastroenterol. 1998; 93: 1919-1924
        • Louw JA
        • Van Rensburg CJ
        • Hanslo D
        • et al.
        Two-week course of pantoprazole combined with 1 week of amoxycillin and clarithromycin is effective in Helicobacter pylori eradication and duodenal ulcer healing.
        Aliment Pharmacol Ther. 1998; 12: 545-550
        • Pazzi P
        • Scagliarini R
        • Gamberini S
        • et al.
        Short-term, low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients.
        Aliment Pharmacol Ther. 1998; 12: 731-734
        • Korman MG
        • Bolin TD
        • Nicholson FB
        • Engelman JL
        Lansoprazole quadruple therapy is effective in curing Helicobacter pylori.
        Helicobacter. 1998; 3: 202-205
        • Langtry HD
        • Wilde MI
        Omeprazole: A review of its use in Helicobacter pylori infection, gastro-oesophageal reflux disease and peptic ulcers induced by nonsteroidal anti-inflammatory drugs.
        Drugs. 1998; 56: 447-486
        • Mears JM
        • Kaplan B
        Proton pump inhibitors: New drugs and indications.
        Am Fam Phys. 1996; 53: 285-292
        • Humphries T
        A review of the drug-drug interaction potential of rabeprazole sodium based on CYP-450 interference or absorption effects.
        Digestion. 1998; 59 (Suppl) (Abstract): 76