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Comparison of rabeprazole 10 mg with esomeprazole 20 mg in the control of gastric PH in healthy volunteers
AJG – September, Suppl., 2001
Abstracts
diabetic NOD gastric muscles by immunohistochemistry using polyclonal antibodies (Santa Cruz Biotechnology). ICC and enteric neurons were identified by antibodies against Kit (ACK2) and protein gene product 9.5 (PGP 9.5; Biogenesis), respectively. Immunoreactivity was visualized with the aid of secondary antibodies tagged with Alexa Fluor 488 and 594 (Molecular Probes) and confocal microscopy (Bio-Rad). Results: IR␣-, IR-, IGF-IR␣- and SCF-like immunoreactivities (-LI) were detected in both circular and longitudinal smooth muscle cells. Myenteric ganglia, nerve trunks and intramuscular nerve fibers were also prominently stained with antibodies to IR subunits, while SCF-LI was only detected in a smaller number of neuronal perikarya. Labeling of ICC was not observed in any specimen. Conclusions: We conclude that smooth muscle cells and enteric neurons, but not ICC, are direct targets of insulin or IGF-I signaling. Absolute or relative insulin or IGF-I insufficiency may, however, lead to ICC depletion via altered SCF expression by smooth muscle cells or enteric neurons. Supported by NIH Grants DK-40569 and DK-41315 to KMS. 247 Comparison of rabeprazole 10 mg with esomeprazole 20 mg in the control of gastric PH in healthy volunteers Steven J Warrington, MD1*, Bina Tejura, MD1, Kathy J Baisley, MPH1, Anna Morocutti, MD2 and Neil M Miller, BSc2. 1Hammersmith Medicines Research, London, United Kingdom; and 2Eisai Ltd., London, United Kingdom. Purpose: To compare the effects of 5 once-daily doses of rabeprazole (RAB) and esomeprazole (ESO) on intragastric pH in healthy H. pylorinegative volunteers. Methods: In a 2-way crossover repeat-dose study comparing RAB 10 mg qd and ESO 20 mg qd, 30 subjects underwent two 5-day treatment periods separated by a 14-day washout. Intragastric pH was recorded over 24 hours on Day 0, 1, and 5 of each period. Percentage of time that pH was ⬎3 and ⬎4, and area under the intragastric pH-time curve from 0-24 hours (AUC0 – 24), were calculated, and compared using ANOVA. Results: There were no statistically significant differences in AUC0 –24 between RAB and ESO treatments on Days 0, 1, or 5 (p ⱖ 0.12; see table of mean (SD)). Furthermore, there were no differences between treatments in percent time that pH was ⬎3 and ⬎4 on Day 1 (percentages arcsin transformed: p ⱖ 0.53). On Day 5, percent time pH ⬎4 was slightly greater on ESO 20 mg than on RAB 10 mg (percentages arcsin transformed: p ⫽ 0.14). Conclusions: At the studied dose levels, there were no differences between RAB and ESO on Day 1 of treatment. On Day 5, ESO increased pH slightly more than did RAB. Day 0 RAB
Day 1 ESO
RAB
Day 5 ESO
RAB
ESO
206304 200876 264552 258466 332762 347728 (40830) (31681) (56522) (63004) (660136) (56356) % time pH 22.0 (12.4) 20.0 (9.6) 42.8 (18.7) 41.2 (20.3) 59.7 (14.0) 64.6 (15.8) ⬎3 % time pH 13.9 (9.8) 12.0 (7.7) 31.2 (16.5) 30.5 (19.9) 48.2 (16.8) 55.0 (16.3) ⬎4
AUC0–24
248 Cardia post Barrett’s ablation: An unrecognized source of concern Allan P Weston1*, Prateek Sharma1 and Magaretia Topalovski1. 1GI, VAMC, Kansas City, MO, United States; and 2Medicine, Univ Kansas Medical Center, Kansas City, KS, United States. Purpose: Thermal ablation of Barrett’s esophagus (BE) is being increasing performed in an effort to destroy the metaplastic mucosa and generate regrowth of squamous epithelium. Valid concerns have been raised with respect to the pesistence of columnar epithelium beneath squamous regrowth with its potential for malignant transformation. However, no reports examine cardia histology post ablation. The aim of this ongoing prospec-
S79
tive study was to examine the endoscopic appearance and histology of the cardia, pre versus post BE ablation. Methods: Several prospective studies have been conducted at our institution with respect to thermal ablation of BE without dysplasia, with LGD, HGD or Tis. In each of these studies, jumbo biopsies of the cardia have been obtained prior to and following complete BE ablation. 4 quadrant biopsies were obtained immediately below the GEJ, fixed in formalin or Bouin’s, stained with H&E with alcian blue pH 2.5. A single pathologists (MT) graded cardia histology for presence and extent of intestinal metaplasia (IM) and dysplasia. Post ablation, all patients have remained on daily PPI therapy. Results: 57 patients have entered into one of the ongoing BE ablation protocols. Of these, 23 have had: a) complete ablation of BE, b) postablation cardia biopsy sampling. All 23 patients were males, age 58.9 ⫾ 12.9. Pre-ablation endoscopic examination of cardia was normal in all with cardia histology revealing rare to focal IM in 2 patients. Post-ablation follow-up ranges from 6 to 48 months (mean ⫾ SD of 18.7 ⫾ 12.3). Post-ablation cardia histologic outcome: 7/23 (30.4%) have cardia IM. IM was a new finding in 5 patients, whereas in 2 others the % of glandular epithelium harboring IM had advanced. In these 7 cardia IM patients, marked atypia was noted in 2, LGD in 1 and HGD in 1. Two of the 7 cardia IM patients had endoscopically visible, small ⬍ 1 cm cardia nodules: EMR of these nodules showed a tubular adenoma with HGD in one and marked atypia in the other. Conclusions: Cardia histology exhibits a disturbing advancement in histology in a significant proportion of patients post ablation, occassionally accompanied by endoscopically visible lesions (nodules). The pathophysiology of why cardia mucosal histology advances post-ablation is unclear but demands further investigation as cardia dysplasia may be a marker for progression to cardia cancer. 249 Effect of eradicating H. pylori infection on intragastric acidity and plasma gastrin during dosing with placebo, lansoprazone, omeprazole, and rabeprazole Matthew P Williams1, Bernard Usselmann2, Judy Sercombe1, Andrew Chilton2, Chuka U Nwokolo2* and Roy E Pounder FACG1. 1 Gastroenterology, Royal Free and University College Hospital Medical School, London, United Kingdom; and 2Gastroenterology, Walsgrave Hospital, Coventry, United Kingdom. Purpose: To compare the effect of eradicating H. pylori (Hp) on 24-h intragastric acidity and 5-h plasma gastrin concentration during lansoprazole, omeprazole and rabeprazole dosing, in a randomised, placebo-controlled trial. Methods: 24 healthy Hp-infected volunteers were studied on the 7th day of dosing with placebo, lansoprazole 30 mg, omeprazole 20 mg and rabeprazole 20 mg, once daily, pre- and at least 5 weeks post-Hp eradication. On each occasion hourly intragastric acidity was measured for 24 hours from 08.00h by gastric aspiration. Plasma gastrin concentrations were measured hourly from 08.00 to 13.00h. Results: 16 subjects completed the study. For all 3 drugs and placebo, Hp eradication increased median integrated acidity, particularly nocturnal acidity, and decreased median integrated gastrin.
Lansoprazole Omeprazole Rabeprazole Placebo
Before After Before After Before After Before After
24-h Acidity (mmol.h/L)
Nocturnal Acidity (mmol.h/L)
5-h Gastrin (pmol.h/L)
27.1 97.1* 18.1 121.9* 12.7 83.8* 636.5 672.5
24.0 78.9* 18.0 99.8* 5.4 69.6* 314.7 442.3*
542.3 399.6* 428.4 267.5* 483.4 328.4 226.1 118.7*
* p ⬍ 0.05, Before vs After There were no differences between the 3 drugs with respect to integrated acidity, % time pH ⬎4 or integrated plasma gastrin, pre- or post-Hp eradication. Nocturnal % time pH ⬎3 was significantly greater during rabeprazole dosing compared to lansoprazole, pre-eradication.
Abstracts
diabetic NOD gastric muscles by immunohistochemistry using polyclonal antibodies (Santa Cruz Biotechnology). ICC and enteric neurons were identified by antibodies against Kit (ACK2) and protein gene product 9.5 (PGP 9.5; Biogenesis), respectively. Immunoreactivity was visualized with the aid of secondary antibodies tagged with Alexa Fluor 488 and 594 (Molecular Probes) and confocal microscopy (Bio-Rad). Results: IR␣-, IR-, IGF-IR␣- and SCF-like immunoreactivities (-LI) were detected in both circular and longitudinal smooth muscle cells. Myenteric ganglia, nerve trunks and intramuscular nerve fibers were also prominently stained with antibodies to IR subunits, while SCF-LI was only detected in a smaller number of neuronal perikarya. Labeling of ICC was not observed in any specimen. Conclusions: We conclude that smooth muscle cells and enteric neurons, but not ICC, are direct targets of insulin or IGF-I signaling. Absolute or relative insulin or IGF-I insufficiency may, however, lead to ICC depletion via altered SCF expression by smooth muscle cells or enteric neurons. Supported by NIH Grants DK-40569 and DK-41315 to KMS. 247 Comparison of rabeprazole 10 mg with esomeprazole 20 mg in the control of gastric PH in healthy volunteers Steven J Warrington, MD1*, Bina Tejura, MD1, Kathy J Baisley, MPH1, Anna Morocutti, MD2 and Neil M Miller, BSc2. 1Hammersmith Medicines Research, London, United Kingdom; and 2Eisai Ltd., London, United Kingdom. Purpose: To compare the effects of 5 once-daily doses of rabeprazole (RAB) and esomeprazole (ESO) on intragastric pH in healthy H. pylorinegative volunteers. Methods: In a 2-way crossover repeat-dose study comparing RAB 10 mg qd and ESO 20 mg qd, 30 subjects underwent two 5-day treatment periods separated by a 14-day washout. Intragastric pH was recorded over 24 hours on Day 0, 1, and 5 of each period. Percentage of time that pH was ⬎3 and ⬎4, and area under the intragastric pH-time curve from 0-24 hours (AUC0 – 24), were calculated, and compared using ANOVA. Results: There were no statistically significant differences in AUC0 –24 between RAB and ESO treatments on Days 0, 1, or 5 (p ⱖ 0.12; see table of mean (SD)). Furthermore, there were no differences between treatments in percent time that pH was ⬎3 and ⬎4 on Day 1 (percentages arcsin transformed: p ⱖ 0.53). On Day 5, percent time pH ⬎4 was slightly greater on ESO 20 mg than on RAB 10 mg (percentages arcsin transformed: p ⫽ 0.14). Conclusions: At the studied dose levels, there were no differences between RAB and ESO on Day 1 of treatment. On Day 5, ESO increased pH slightly more than did RAB. Day 0 RAB
Day 1 ESO
RAB
Day 5 ESO
RAB
ESO
206304 200876 264552 258466 332762 347728 (40830) (31681) (56522) (63004) (660136) (56356) % time pH 22.0 (12.4) 20.0 (9.6) 42.8 (18.7) 41.2 (20.3) 59.7 (14.0) 64.6 (15.8) ⬎3 % time pH 13.9 (9.8) 12.0 (7.7) 31.2 (16.5) 30.5 (19.9) 48.2 (16.8) 55.0 (16.3) ⬎4
AUC0–24
248 Cardia post Barrett’s ablation: An unrecognized source of concern Allan P Weston1*, Prateek Sharma1 and Magaretia Topalovski1. 1GI, VAMC, Kansas City, MO, United States; and 2Medicine, Univ Kansas Medical Center, Kansas City, KS, United States. Purpose: Thermal ablation of Barrett’s esophagus (BE) is being increasing performed in an effort to destroy the metaplastic mucosa and generate regrowth of squamous epithelium. Valid concerns have been raised with respect to the pesistence of columnar epithelium beneath squamous regrowth with its potential for malignant transformation. However, no reports examine cardia histology post ablation. The aim of this ongoing prospec-
S79
tive study was to examine the endoscopic appearance and histology of the cardia, pre versus post BE ablation. Methods: Several prospective studies have been conducted at our institution with respect to thermal ablation of BE without dysplasia, with LGD, HGD or Tis. In each of these studies, jumbo biopsies of the cardia have been obtained prior to and following complete BE ablation. 4 quadrant biopsies were obtained immediately below the GEJ, fixed in formalin or Bouin’s, stained with H&E with alcian blue pH 2.5. A single pathologists (MT) graded cardia histology for presence and extent of intestinal metaplasia (IM) and dysplasia. Post ablation, all patients have remained on daily PPI therapy. Results: 57 patients have entered into one of the ongoing BE ablation protocols. Of these, 23 have had: a) complete ablation of BE, b) postablation cardia biopsy sampling. All 23 patients were males, age 58.9 ⫾ 12.9. Pre-ablation endoscopic examination of cardia was normal in all with cardia histology revealing rare to focal IM in 2 patients. Post-ablation follow-up ranges from 6 to 48 months (mean ⫾ SD of 18.7 ⫾ 12.3). Post-ablation cardia histologic outcome: 7/23 (30.4%) have cardia IM. IM was a new finding in 5 patients, whereas in 2 others the % of glandular epithelium harboring IM had advanced. In these 7 cardia IM patients, marked atypia was noted in 2, LGD in 1 and HGD in 1. Two of the 7 cardia IM patients had endoscopically visible, small ⬍ 1 cm cardia nodules: EMR of these nodules showed a tubular adenoma with HGD in one and marked atypia in the other. Conclusions: Cardia histology exhibits a disturbing advancement in histology in a significant proportion of patients post ablation, occassionally accompanied by endoscopically visible lesions (nodules). The pathophysiology of why cardia mucosal histology advances post-ablation is unclear but demands further investigation as cardia dysplasia may be a marker for progression to cardia cancer. 249 Effect of eradicating H. pylori infection on intragastric acidity and plasma gastrin during dosing with placebo, lansoprazone, omeprazole, and rabeprazole Matthew P Williams1, Bernard Usselmann2, Judy Sercombe1, Andrew Chilton2, Chuka U Nwokolo2* and Roy E Pounder FACG1. 1 Gastroenterology, Royal Free and University College Hospital Medical School, London, United Kingdom; and 2Gastroenterology, Walsgrave Hospital, Coventry, United Kingdom. Purpose: To compare the effect of eradicating H. pylori (Hp) on 24-h intragastric acidity and 5-h plasma gastrin concentration during lansoprazole, omeprazole and rabeprazole dosing, in a randomised, placebo-controlled trial. Methods: 24 healthy Hp-infected volunteers were studied on the 7th day of dosing with placebo, lansoprazole 30 mg, omeprazole 20 mg and rabeprazole 20 mg, once daily, pre- and at least 5 weeks post-Hp eradication. On each occasion hourly intragastric acidity was measured for 24 hours from 08.00h by gastric aspiration. Plasma gastrin concentrations were measured hourly from 08.00 to 13.00h. Results: 16 subjects completed the study. For all 3 drugs and placebo, Hp eradication increased median integrated acidity, particularly nocturnal acidity, and decreased median integrated gastrin.
Lansoprazole Omeprazole Rabeprazole Placebo
Before After Before After Before After Before After
24-h Acidity (mmol.h/L)
Nocturnal Acidity (mmol.h/L)
5-h Gastrin (pmol.h/L)
27.1 97.1* 18.1 121.9* 12.7 83.8* 636.5 672.5
24.0 78.9* 18.0 99.8* 5.4 69.6* 314.7 442.3*
542.3 399.6* 428.4 267.5* 483.4 328.4 226.1 118.7*
* p ⬍ 0.05, Before vs After There were no differences between the 3 drugs with respect to integrated acidity, % time pH ⬎4 or integrated plasma gastrin, pre- or post-Hp eradication. Nocturnal % time pH ⬎3 was significantly greater during rabeprazole dosing compared to lansoprazole, pre-eradication.