Abstract
Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole.
Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10,20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20mg twice daily plus 2 antibacterial agents achieved ≥90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication.
Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome.
Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events.
In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.
Pharmacodynamic Effects
Rabeprazole interacts at the same site on the proton pump as omeprazole, but did not produce conformational changes in the protein in an in vitro study. The effects of rabeprazole on acid secretion are dose dependent over dosages from 5 to 40 mg/day in volunteers. Importantly, an increase in gastric pH, coupled with a reduction in oesophageal acid exposure, was seen in patients with GERD who received rabeprazole 20 or 40mg once daily for 7 days.
In volunteers, 24-hour acidity on day 1 was significantly lower with rabeprazole 20mg/day than omeprazole 20mg/day (p < 0.001).
Increases in gastrin after rabeprazole administration were dose dependent and directly related to increases in gastric pH. In clinical trials, rabeprazole appeared to produce greater increases in fasting serum gastrin levels than omeprazole in patients with duodenal ulcers, but had similar effects to omeprazole in patients with gastric ulcers or GERD. In these trials serum gastrin levels at endpoint did not exceed 3 times the upper limit of normal in patients with normal levels at baseline.
Rabeprazole and amoxicillin had at most additive effects on H. pylori isolates in vitro; however, synergistic anti-H. pylori effects were seen when the thioether metabolite of rabeprazole was combined with amoxicillin. H. pylori urease protects the micro-organism from gastric acid, but is inhibited in vitro at lower concentrations of rabeprazole than of lansoprazole or omeprazole. Rabeprazole does not appear to differ from other proton pump inhibitors in its ability to affect gastric cells. Long term rodent carcinogenicity studies have shown the potential for rabeprazole to cause enterochromaffin-like cell hyperplasia without causing more severe proliferative changes. Unlike omeprazole (which reduced gastric mucin) and lansoprazole (which had no effect), rabeprazole was reported to significantly increase the production of gastric mucin (a defensive factor) in rats. Like omeprazole, rabeprazole prevented or reduced the size of gastric ulcers caused by water immersion in rats, and prevented stress-induced increases in gastric mucosal peptide-leukotriene content without altering mucosal prostaglandin levels. Rabeprazole, unlike omeprazole, had no effect on steroido-genesis or other aspects of endocrine function.
Pharmacokinetic Properties
Pharmacokinetic studies of rabeprazole 1 to 80mg in single and multiple doses have been conducted in volunteers. Both the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) for rabeprazole were roughly proportional to the dose after single oral doses of 10 to 80mg. The time to reach the rabeprazole Cmax(tmax) was 2.9 to 3.8 hours after administration of single doses of 10 to 80mg and was independent of the dose. Rabeprazole absorption pharmacokinetic s were generally similar after single and multiple daily 20 and 40mg doses. The drug was 96.3% bound to plasma proteins.
Rabeprazole is rapidly cleared by hepatic metabolism and renal excretion. The drug has an elimination half-life of ≈1 hour and an apparent oral clearance ranging from 0.26 to 0.50 L/h/kg (4.3 to 8.4 ml/min/kg) which was not dependent on the dose from 10 to 80mg. Rabeprazole is metabolised by human cytochrome P450 enzymes CYP2C19 and CYP3A to demethyl and sulfone metabolites. The major metabolite is a thioether carboxylic acid compound. The interaction of rabeprazole with CYP2C19 was less than that of omeprazole and interaction with CYP3A was similar to or lower than the low level of interaction seen with omeprazole. There were no clinically significant changes in pharmacokinetic parameters when rabeprazole was administered to patients with renal or hepatic dysfunction or elderly individuals.
Absorption of rabeprazole was unaffected by concomitant or prior administration of an aluminum hydroxide/magnesium hydroxide antacid preparation, whereas administration of rabeprazole with food delayed the tmax by 1.7 hours. In interaction studies in volunteers, rabeprazole had no significant effects on most cytochrome P450 enzyme systems, although predictable interactions occurred with ketoconazole and digoxin as a result of rabeprazole-induced changes in gastric pH.
Clinical Efficacy
The efficacy of rabeprazole has been studied in patients with duodenal or gastric ulcers, GERD, Zollinger-Ellison syndrome and H. pylori infection.
In 3 well controlled 4-week studies in patients with duodenal ulcers, rabeprazole 20 and 40 mg/day were compared with placebo, and rabeprazole 20 mg/ day was compared with omeprazole 20 mg/day or ranitidine 150mg twice daily. Rabeprazole healed duodenal ulcers faster than placebo or ranitidine and at a generally similar healing rate to omeprazole in patients with duodenal ulcers. The relief of overall and day or night-time symptoms with rabeprazole in 4-week trials in patients with duodenal ulcers was similar or superior to that provided by placebo, ranitidine or omeprazole.
In 2 well controlled 6-week studies in patients with benign gastric ulcers, rabeprazole 20 and 40 mg/day dosages were compared with placebo and rabeprazole 20 mg/day was compared with omeprazole 20 mg/day. Rabeprazole healed ulcers faster than placebo and at a similar healing rate to omeprazole in patients with gastric ulcers. The relief of symptoms provided by rabeprazole in 6-week trials in patients with gastric ulcers was similar or superior to that provided by placebo or omeprazole. Day pain at 3 weeks, pain frequency at 6 weeks and night pain at 6 weeks were all significantly less common or severe with rabeprazole than omeprazole in a trial in 127 patients.
The efficacy of rabeprazole in achieving healing and the relief of symptoms of erosive or ulcerative GERD has been tested in 4 well controlled 8-week clinical trials comparing it with placebo, omeprazole or ranitidine. Rabeprazole 10, 20 and 40 mg/day doses (8-week healing rates 93, 84 and 85%) were more effective than placebo (12%, p < 0.001) and rabeprazole 20 mg/day (4- and 8-week healing rates 58 and 88%) was more effective than ranitidine 150mg 4 times daily (36 and 65%, p < 0.001). Eight-week healing rates were similar after rabeprazole 20mg once daily (92 or 97%) or 10mg twice daily (98%) and omeprazole 20 mg/day (94 or 100%) in 2 studies. Symptom relief with rabeprazole in 8-week trials in patients with GERD was similar or superior to that provided by placebo, ranitidine or omeprazole.
Two 1-year trials examined the efficacy of rabeprazole 10 and 20 mg/day compared with placebo or omeprazole in maintaining healing and symptom relief in patients following healing of grades 2 to 4 GERD. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD.
In two 1-week pilot studies, rabeprazole 20mg twice daily significantly improved H. pylori eradication when added to a regimen of amoxicillin 500mg 4 times daily. In a larger study, 1-week triple therapy with rabeprazole 20mg twice daily plus 2 of clarithromycin 500mg twice daily, metronidazole 400mg twice daily or amoxicillin 1g twice daily achieved ≥90% H. pylori eradication, but rabeprazole 20mg twice daily plus clarithromycin 500mg once daily was less successful (63% eradication). Rabeprazole 20mg twice daily was as effective as omeprazole 20mg twice daily and lansoprazole 30mg twice daily as part of 1-week triple therapy for H. pylori infection, in a randomised study. Each antisecretory drug was combined with amoxicillin 1500 mg/day and clarithromcyin 400 mg/day. Intention to treat cure rates were 87.5% in the rabeprazole group versus 85.3 and 83.8% in the omeprazole and lansoprazole groups, respectively.
In a nonblind comparative 12-month study in 10 patients with hypersecretory conditions (age 41 to 75 years), rabeprazole successfully reduced acid output to target levels and prevented further pathological changes. Patients with Zollinger-Ellison syndrome and idiopathic gastric hypersecretion received rabeprazole 60 mg/day, with 1 patient requiring rabeprazole, 60mg twice, daily.
Tolerability
Rabeprazole was well tolerated in comparative trials of up to 1 year in duration enroling a total of >2500 patients, with tolerability that was not significantly different from that seen with in patients receiving placebo, omeprazole or ranitidine. The most common adverse events in clinical trials were headache, rash, infection, diarrhoea and flu syndrome, each of which was present in <5% of patients.
Dosage and Administration
The usual oral dosage of rabeprazole is 20 mg/day, although some patients with Administration duodenal ulcer may respond to 10 mg/day. Usual durations of rabeprazole therapy are 4 weeks for duodenal ulcer healing, 6 weeks for gastric ulcer healing, 8 weeks for healing and symptom relief for erosive or ulcerative GERD and long term (>1 year) for maintenance of GERD healing or for hypersecretory conditions such as Zollinger-Ellison Syndrome. In patients with H. pylori infection, rabeprazole 20 mg/day is usually administered with 2 antibacterial agents for 1 week. Patients with Zollinger-Ellison syndrome usually require rabeprazole 60 mg/day, although larger dosages (e.g. 60mg twice daily) have been used in clinical practice. Rabeprazole can alter concentrations of ketoconazole and digoxin because of the dependency of these drugs on gastric pH for absorption.
Similar content being viewed by others
References
Wilde MI, McTavish D. Omeprazole: an update of its pharmacology and therapeutic use in acid-related disorders. Drugs 1994 Jul; 48: 91–132
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 Sep; 56: 447–86
Langtry HD, Wilde MI. Lansoprazole: an update of its pharmacological properties and clinical efficacy in the management of acid-related disorders. Drugs 1997 Sep; 54: 473–500
Fitton A, Wiseman L. Pantoprazole: a review of its pharmacological properties and therapeutic use in acid-related disorders. Drugs 1996 Mar; 51: 460–82
Berardi RR, Welage LS. Proton-pump inhibitors in acid-related diseases. Am J Health System Pharm 1998 Nov 1; 55: 2289–98
Humphries TJ, Barth J. Review article: rabeprazole’s profile in patients with gastrointestinal diseases. Aliment Pharmacol Ther 1999; 13 Suppl. 5. In press
Morii M, Takeguchi N. Different biochemical modes of action of two irreversible H+,K+-ATPase inhibitors, omeprazole and E 3810. J Biol Chem 1993 Oct 15; 268: 21553–9
Morii M, Takeguchi N. The binding site of E3810 to gastric proton pump [abstract]. 10th World Congress of Gastroenterology; 1994 Oct 2–9: Los Angeles (CA), 1995P
Morii M, Takeguchi N. The conformational state of proton pump is differently affected by omeprazole, lansoprazole and E3810 [abstract]. 10th World Congress of Gastroenterology; 1994 Oct 2–9: Los Angeles (CA), 1994P
Morii M, Takata H, Fujisaki H, et al. The potency of substituted benzimidazoles such as E3810, omeprazole, Ro-18-5364 to inhibit gastric H+,K+-ATPase is correlated with the rate of acid-activation of the inhibitor. Biochem Pharmacol 1990 Feb 15; 39: 661–7
Shibata H, Murakmai M, Fujimoto M, et al. Histamine-stimulated gastric acid secretion is inhibited in gastric fistula dogs treated with E3810 (2-[4-(3-methoxypropoxy)-3-methylpyridin-2-ylmethyl sulfinyl]-1H-benzim idazole, sodium) [abstract]. FASEB J 1990 Feb 26; 4: A473
Takeguchi N, Tomiyama Y, Morii M. The intracellular cycling of gastric proton pump is differently affected by E3810 and lansoprazole in rats [abstract]. 10th World Congress of Gastroenterology; 1994 Oct 2–9: Los Angeles (CA), 1996P
Inoue M, Shirakawa T, Murakami Y, et al. Effect of a new proton pump inhibitor E3810 on intragastric pH in the patients with peptic ulcer [abstract]. Gastroenterology 1991 May; 100 Suppl.: 89
Williams MP, Sercombe J, Hamilton MI, et al. 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 Nov; 12: 1079–89
Kovacs TOG, Sytnik B, Humphries TJ, et al. A low dose of a new proton pump inhibitor LY-307640 (E3810) effectively inhibits acid secretion in humans [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A161
Lew EA, Barbuti RC, Kovacs TOG, et al. An ascending single-dose safety and tolerance study of an oral formulation of rabeprazole (E3810). Aliment Pharmacol Ther 1998 Jul; 12: 667–72
Robinson M, Maton PN, Rodriguez S. Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastrooesophageal reflux disease. Aliment Pharmacol Ther 1997 Oct; 11: 973–80
Pounder RE, Blanshard C, Millson C, et al. Effects of rabeprazole on 24-hour intragastric acidity and plasma gastrin in healthy subjects [abstract]. 98th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics; 1997 Mar 5–8: San Diego (CA), 169
Bell NE, Humphries TJ. Comparison of fasting serum gastrin levels in 634 patients treated with either rabeprazole 20mg or omeprazole 20mg once daily in 3 double-blind therapeutic trials [abstract]. Gastroenterology 1997 Apr; 112(4) Suppl.: A70
Humphries T, Dekkers C, Beker J, et al. Magnitude of changes in fasting serum gastrin in 211 patients taking rabeprazole 10 mg or 20 mg or omeprazole 20 mg for one year [abstract]. Am J Gastroenterol 1998 Sep; 93: 1637
Fujiyama K, Fujioka T, Kodama R, et al. Effect of E3810, a novel proton pump inhibitor, against Helicobacter pylori [abstract]. Am J Gastroenterol 1994 Aug; A89: 1371
Satoh M, Tonomura H, Murakami M, et al. In vitro activity of E3810/LY307640, a novel proton pump inhibitor, against Helicobacter pylori [abstract]. 10th World Congress of Gastroenterology; 1994 Oct 2–9: Los Angeles (CA), 196P
Moore R, Bryan LE, Satoh M, et al. Anti-Helicobacter pylori activity synergy between amoxicillin and the thioether derivative of the proton pump inhibitor E3810/LY307640 [abstract]. 10th World Congress of Gastroenterology; 1994 Oct 2–9: Los Angeles (CA), 197P
Tsuchiya M, Imamura L, Park JB, et al. Helicobacter pylori urease inhibition by rabeprazole, a proton pump inhibitor. Biol Pharm Bull 1995 Aug; 18: 1053–6
Park JB, Imamura L, Kobashi K. Kinetic studies of Helicobacter pylori urease inhibition by a novel proton pump inhibitor, rabeprazole. Biol Pharm Bull 1996 Feb; 19: 182–7
Pospai D, Cadiot G, Vissuzaine C, et al. Fundic mucosa of GER patients continuously treated with ranitidine: comparison with omeprazole-treated patients and controls [abstract]. Gastroenterology 1995; 108(4): A194
Anonymous. Proton pump inhibitor relabeling for cancer risk not warranted. FDC Rep Pink Sheet 1996 Nov 11; 58: 1–2
Humphries TJ. Rabeprazole sodium: is it possible to improve the benefit risk equation for proton pump inhibitors (PPI)? Gut 1996 Nov; 39: A777
Humphries T, Rindi G, Fiocca R. Argyrophil ECL cell histology in the gastric corpus and antrum in 243 patients taking rabeprazole 10 mg or 20 mg or omeprazole 20 mg for one year [abstract]. Am J Gastroenterol 1998 Sep; 93: 1637
Takiuchi H, Asada S, Umegaki E, et al. Effects of proton pump inhibitors, omeprazole, lansoprazole and E-3810, on the gastrin mucin [abstract]. 10th World Congress of Gastroenterology; 1994 Oct 2–9: Los Angeles (CA), 1404P
Goto H, Tsukamoto Y, Ohara A, et al. Effects of decreased leukotrienes by proton pump inhibitors on water immersion stress-induced gastric ulcers in rats [abstract]. Gastroenterology 1992 Apr; 102 (Pt 2): A75
Dammann HG, Burkhardt F, Bell NE, et al. Rabeprazole does not affect endocrine function in healthy subjects [abstract no. 646]. Am J Gastroenterol 1996 Sep; 91: 1909
Takakuwa S, Chiku S, Nakata H, et al. Enantioselective pharmacokinetics of E3810, a new anti-ulcer agent, in dogs and rats [abstract]. 7th North American Meeting of the International Society for the Study of Xenobiotics; 1996 Oct 19–24: San Diego, (CA); 10: 346
Yasuda S, Ohnishi A, Ogawa T, et al. Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers. Int J Clin Pharmacol Ther 1994 Sep; 32: 466–73
Nakai H, Shimamura Y, Kanazawa T, et al. Determination of a new H+-K+ ATPase inhibitor (E3810) and its four metabolites in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Appl 1994 Oct 3; 660: 211–20
VandenBranden M, Ring BJ, Binkley SN, et al. Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump inhibitor. Pharmacogenetics 1996 Feb; 6: 81–91
Yasuda S, Horai Y, Tomono Y, et al. Comparison of the kinetic disposition and metabolism of E3810, a new proton pump inhibitor, and omeprazole in relation to 5-mephenytoin 4′-hydroxylation status. Clin Pharmacol Ther 1995 Aug; 58: 143–54
Ishizaki T, Chiba K, Manabe K, et al. Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of 5-mephenytoin 4′-hydroxylation. Clin Pharmacol Ther 1995 Aug; 58: 155–64
Fujisaki H, Oketani K, Nagakawa J-i, et al. Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic lysosomal enzymes in rats. Jpn J Pharmacol 1998 Mar; 76: 279–88
Spera A, Merritt J, Keane W, et al. Rabeprazole 20mg does not appear to require dosage adjustment in elderly patients or those with renal or hepatic disease [abstract no. ExhB1069]. Digestion 1998; 59 Suppl. 3: 76
Hoyumpa AM, Trevino-Alanis H, Grimes I, et al. Rabeprazole: pharmacokinetics in patients with stable compensated cirrhosis. Clin Ther 1999 Apr; 21(4): 691–701
Laurent AL, Merritt GJ, Setoyama T, et al. Rabeprazole: pharmacokinetics and safety in the elderly. Clin Geriatr 1999 May; 7(6): 27–33
Humphries TJ, Keane WF, St. Peter JV, et al. Rabeprazole, safety, tolerance, and pharmacokinetics in patients with renal dysfunction [abstract]. Am J Gastroenterol 1998; 93(9): 1638
Yasuda S, Higashi S, Murakami M, et al. Antacids have no influence on the pharmacokinetics of rabeprazole, a new proton pump inhibitor, in healthy volunteers. Int J Clin Pharmacol Ther 1998; 37(5): 249–53
Humphries TJ, Nardi RV, Lazar JD, et al. Drug-drug interaction evaluation of rabeprazole sodium: a clean/expected slate? [abstract]. Gut 1996; 39 Suppl. 3: A47
Cloud ML, Enas N, Humphries TJ, et al. Rabeprazole in treatment of acid peptic diseases: results of three placebo-controlled dose-response clinical trials in duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease (GERD). Dig Dis Sci 1998 May; 43: 993–1000
Dekkers CPM, Beker JA, Thjodleifsson B, et al. Comparison of rabeprazole 20mg versus omeprazole 20mg in the treatment of active duodenal ulcer: a European multicentre study. Aliment Pharmacol Ther 1999; 13: 179–86
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 [abstract]. Gastroenterology 1997 Apr; 112(4) Suppl.: A154
Dekkers CP, Beker JA, Thjodleifsson B, et al. Comparison of rabeprazole 20mg vs. omeprazole 20mg in the treatment of active gastric ulcer — a European multicentre study. The European Rabeprazole Study Group. Aliment Pharmacol Ther 1998 Aug; 12: 789–95
Dekkers CPM, Beker JA, Thjodleifsson B, et al. Double-blind, placebo-controlled comparison of rabeprazole 20mg vs. omeprazole 20mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1999 Jan; 13: 49–57
Delchier JC, Cohen G, Humphries TJ, et al. Rabeprazole is comparable in efficacy to omeprazole in erosive GORD and provides more rapid heartburn relief [abstract no. TH446]. Gut 1999;44 Suppl. 1: A112
Humphries TJ, Spera A, Breiter J, et al. Rabeprazole sodium (E3810) once daily is superior to ranitidine 150 mg QID in the healing of erosive or ulcerative gastroesophageal reflux disease [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: A139
Birbara C, Breiter J, Collins D, et al. Rabeprazole: preventing endoscopic and symptomatic relapse in erosive or ulcerative GERD [abstract]. Am J Gastroenterol 1998 Sep; 93: 1630
Humphries TJ, Dekkers CPM, Beker JA, et al. Rabeprazole vs omeprazole for maintenance therapy of healed erosive GERD: results of a 1-year multicenter trial [abstract]. Am J Gastroenterol 1998 Sep; 93: 1616
Humphries TJ, Bassion S, Spanyers SA. Pilot studies on the effects of rabeprazole sodium (E3810), amoxicillin, and placebo on the eradication of H. pylori [abstract]. Am J Gastroenterol 1996 Sep; 91: 1914
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 Oct;93: 1909–13
Miwa H, Ohkura R, Murai T, et al. Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection — comparison with omeprazole and lansoprazole. Aliment Pharmacol Ther 1999; 13: 741–6
Mignon M, Merrouchem M, Gardner J, et al. Rabeprazole therapy effective in Zollinger-Ellison syndrome and idiopathic gastric acid hypersecretion [abstract no. TH500]. Gut 1999 Apr; 44 Suppl. 1: A125
Johnson D, Riff R, Perdomo C, et al. Rabeprazole: safety profile of a new proton pump inhibitor [abstract no. G0875]. Gastroenterology 1999 Apr; 116 (4)
Eisai Ltd. Rabeprazole prescribing information. London. England, 1998
Ikeda S, Ikegami N. Cost-effectiveness of proton pump inhibitors in gastric ulcer [abstract]. Pharmacoepidemiol Drug Saf 1998 Aug; 7 Suppl. 2: S92
Ofman JJ, Yamashita BD, Siddique RS, et al. Cost-effectiveness of rabeprazole versus ranitidine in reflux esophagitis [abstract]. Value in Health 1999 May/Jun; 2(3): 154
Author information
Authors and Affiliations
Corresponding author
Additional information
Various sections of the manuscript reviewed by: S. Bank, Long Island Jewish Medical Center, Division of Gastroenterology, New York, New York, USA; N. Chiba, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; C. Florent, Hôpital Saint Antoine, Paris, France; A.W. Harris, Kent and Sussex Hospital, Tunbridge Wells, England; R.T. Jensen, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA; K. Kobashi, Toyama Medical and Pharmaceutical University, Toyama, Japan; J. Labenz, Jung-Stilling Hospital, Siegen, Germany; M. Robinson, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA; W.A. Stack, Bon Secours Hospital, Cork, Ireland; N. Takeguchi, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan; J.H. Walsh, CURE: Digestive Diseases Research Center, West Los Angeles VA Medical Center, Los Angeles, California, USA.
Rights and permissions
About this article
Cite this article
Langtry, H.D., Markham, A. Rabeprazole. Drugs 58, 725–742 (1999). https://doi.org/10.2165/00003495-199958040-00014
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199958040-00014