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Influence of pantoprazole 40 MG and omeprazole 20 MG on meal-stimulated gastric acid secretion
A98 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 114, No. 4
G0398 INFLUENCE OF PANTOPRAZOLE 40 M G AND OMEPRAZOLE 20 MG ON MEAL-STIMULATED GASTRIC ACID SECRETION. H.G. Dammann, F. Burkhardt, Institute for Clinical Research, Hamburg, FRG. Purpose: The aim of this double-blind, placebo-controlled, three-fold cross-over study was to investigate, by means of meal-stimulated acid secretion, the extent to which differences in plasma half-life, bioavailability and the recommended therapeutic dose can influence the antisecretory potency of pantoprazole (P) and omeprazole (O). Methods: 12 healthy male volunteers (age: 24-35 years) received pantoprazole 40 mg, omeprazole 20 mg or placebo for five consecutive days. The individual treatment periods were separated by a 14 day washout phase. Meal stimulated acid-secretion was measured 24 hours after drug intake on day 1 and 4 hours after drug intake on days 3 and 5 of each treatment period. The pH of a standardized test meal (600 ml) was adjusted to 5 and the meal was infused into the stomach within 5 min. Thereafter the meal was aspirated continuously over 2 hours titrated with 0.1 n NaOH to pH 5 and then reinfused into the stomach. Results: Acid secretion (mmol H+/2h) is summarized in the following table: Day
Placebo
1
21.3)6.8
Pantoprazole 40 nag I1.1)8.1
Omelarazole 2Omg 15.3)8.8
3
26.2 ) 6,9
3.3 ) 3.8
8.5 ) 8.8
5
23.0 ) 6.4
3.5 ) 4.0
6.9 ) 8.9
p < 0.05 sign rank test (two sided, per protocol) On day 1 only P 40 mg was statistically superior to placebo (p < 0.05). On days 3 and 5 both proton pump inhibitors were superior to placebo (p < 0.05), and on days 1 and 3 P 40 mg was superior to 0 20 mg (p < 0.05). Conclusion: This investigation shows a significantly more rapid onset of action and a significantly higher antisecretory potency of pantoprazole compared to omeprazole. • G0399 CELLULAR ORIGIN OF BARRETT'S EPITHELIUM: A CRITICAL ANALYSIS USING A NOVEL BIOMARKER. K.M, Das, N Botros, PS Amenta. UMDNJ-Robert Wood Johnson Medical School and Robert Wood Johnson University Hospital, New Brunswick, NJ. mAb DAS-1 (previously called 7E12H12), is a murine monoclonai antibody (IgM isotype) developed against a colon epithelial glycoprotein (CEP) that reacts specifically with normal colon epithelium, but not with the mucosa from 17 other organs including esophagus, gastroesophageal junction (GEJ), cardia and the rest of stomach and small intestine (J Immunol 1987; 139:77). However, it does react sensitively with Barrett's epithelium (BE) and adenocarcinoma of the esophagus arising from BE (Ann Int Med 1994; 120:753). The cellular origin of BE is unknown. AIM and METHODS: Using this novel mAb, we examined the immunoreactivity of the distal esophagus including the submucosal glands by a sensitive immunoperoxidase assay (IPA). Seventeen surgical specimens of distal esophagus, including GEJ (histologically normal segments), 5 salivary glands (both parotid and minor salivary glands), 3 full thickness gastric mucosa, and 3 duodenal biopsy specimens containing Brunner's glands were analyzed. Only histologically normal areas were selected. In addition to the IPA, serial sections of these specimens were also examined by routine H&E and with alcian blue high iron diamine, pH 2.5 (AB/HID). Three samples of histologically proven BE, with specialized columnar epithelium, were examined in parallel with each experiment as positive control. An unrelated murine MOPC-IgM was used as a negative control. RESULTS: mAb DAS-I stained strongly a small number of glandular epithelial cells in the submucosal glands in the distal esophagus/GEL The staining was intense and was also clearly evident in the ductai epithelium of these glands. However, overlying luminal squamous epithelium or normal GE junctional epithelium and cardia did not react with mAb DAS-1. Each of the 3 BE specimens clearly reacted with the rnAb. mAb DAS-1 did not show any reactivity in the glandular epithelium in any of the salivary glands, gastric and Brunner's glands. However, AB/HID staining was positive in all cells of the esophageal submucosal glands, as well as in the salivary and gastric glands. CONCLUSION: These data indicate phenotypic similarity of BE with specific cells in the submucosal glands/ducts of the distal esophagus/GEJ, suggesting the latter as a potential source of origin of BE. G0400 ULTRA-SHORT COURSE THERAPY FOR ERADICATION OF HELICO. BACTER PYLORI. Jonathan David, M.D., FACP, FACG, Magdi Khalil, M.D., Ben Ten'any, M.D., Lisa A. Ozick, M.D., FACG Columbia University College of Physicians and Surgeons, Harlem Hospital Center, New York, NY Introduction: Standard protocols for eradication of Helicobacter pylori (Hp) require a 14 day course of antibiotics. Certain 7 day drug regimens recently have been shown to be effective, but there has been little published about eradication regimens shorter than 7 days. Aim; To investigate the efficacy and tolerability of an Hp eradication regimen given for 3 or 5 days. Methods: Patients were eligible if they had either a gastric or duodenal ulcer on endoscopy, and Hp found on rapid urease testing and pathology. They
were then randomly assigned (in a 2:2:1 fashion) to either a 3, 5, or 7 day course of quadruple therapy with: omeprazole 40 mg bid, PeptoBismol tablets 2 po qid, tetracycline 500 mg qid, and clarithromycin 500 mg tid. Additional omeprazole 20 mg qd was then given to complete a 4 week course. Follow up endoscopy was done at least 4 weeks after completion of the omeprazole. Successful eradication was defined as a negative rapid urease of biopsies taken from both the antrum and fundus and placed in the same well. The rapid urease tests were read by blinded investigators. Results: Eradication rates were as follows: 3 day ann: 9 of 10 subjects (90%); 5 day arm: 10 of 11 subjects (91%); 7 day arm: 3 of 3 subjects (100%; p=NS vs. 3 day and 5 day groups). All subjects completed their antibiotics without ill effects, but the patient in the 5 day arm who failed eradication did not take omeprazole after the initial 5 day quadruple therapy. Conclusions: This small, preliminary study suggests that "ultra-short course" quadruple therapy for Hp eradication is well tolerated, and that it may be as effective as many accepted regimens of 7 or even 14 days. More research is needed in this area. G0401
HELICOBACTER PYLORI RESISTANCE TO CLARITHROMYCIN, METRONIDAZOLE, AMOXICILLIN, TETRACYCLIN, AND TROVAFLOXACIN I N THE NETHERLANDS. Y.J. Debets-Ossenkopp, A.J. Herscbeid, E.J. Kuipers, J.G. Kusters, C.M.J.E. Vandenbroucke-Grauls. Dept. of Medical Microbiology en Gastroenterology. University Hospital "Vrije Universiteit" P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Clarithromycin and metronidazole are most active in the treatment of infections with 11. pylori and hence frequently used. Successful treatment is becoming more and more compromised by emerging resistance against these two antibiotics. The neomacrolides clarithromycin, azithromycin and roxitromycin have been introduced recently and are used increasingly in the Netherlands. In this study we determined the prevalence of primary antibiotic resistance of H. pylori in the Netherlands. Trovafioxacin is not yet approved for treatment of H. pylori infections but was included in the study because this new quinolone appears a promising candidate for the treatment of H. pylori infections. Clarithromycin, metronidazole, tetracyclin, and amoxicillin were studied, because of their proven value. Methods H. pylori isolates were collected from 18 different medical microbiology laboratories throughout the Netherlands. Each laboratory forwarded between 15 and 20 consecutive isolates from patients presenting for endoscopy between August and November 1997. MIC's for all antibiotics were determined by the E-test. Results: The resistance rate to clarithromycin was low, between 1 and 3% (MIC < 2 mg/L). Resistance rates for metronidazole were as high as 30% (MIC > 32 rag/L). None of the isolates was resistant to tetracyclin or amoxiciUin (all MIC's lower than 2 mg/L and 0.032 mg/L respectively). Breakpoints for trovafloxacin are not available yet, but the MIC's of the isolates varied between 0.016 and 3 mg/L. Con~lusi0n: In the Netherlands, only resistance to metronidazole in H. pylori has reached significant levels. The resistance rate to clarithromycin remains low, while it is non-existent for ampoxicilin and tetracyclin. Trovafloxacin appears a promising agent. G0402
TOWARDS MONOTHERAPY FOR HELICOBACTER PYLORI INFECTION: FIRST RESULTS WITH A SINGLE TRIPLE CAPSULE. de Boer WA, Borody TL Sint Anna Hospital, Oss, The Netherlands and Centre for Digestive Diseases, Sydney, NSW 2046, Australia Two week bismuth triple therapy(Tr) is the oldest effective and most investigated anti-H, pylori therapy. Treatment duration can be reduced to 7 days if a proton pump inhibitor (PPI) is added (Quadruple Therapy) resulting in the highest known cure-rates, usually above 95%. However, patients need to take numerous pills per day and the regimen is perceived as complex. Fear of non-compliance may have delayed its acceptance. Recently an "all in one" triple capsule has became available containing per 2 capsules 108mg of bismuth subcitrate, 500mg of tetracycline HC1 and 250mg of metronidazole. We report on the tolerability and efficacy of this new patient-friendly formulation of bismuth TT. Methods: In an open, two-centre study, consecutive infected patients with ulcer disease or non-ulcer dyspepsia were treated with omeprazole 20mg bd and the 'single triple' 2 capsules qid day 17. H. pylori status was determined before and at least 4 weeks after therapy by endoscopy with at least 3 antral and 2 corpus biopsies for CLO-test, histology and culture. An E-test was used for the antibiogram. Results: 37(19F/18M) patients were included and complete compliance was achieved in 36/37(97%). Tolerability was excellent with one 'drop out' due to allergy with 87% reporting absence of adverse effects. Patients expressed no problems with the size or the number of capsules(10/d). Over-all 33/36 (92%), were cured per protocol(PP) and 33/37(89%) intention to treat. Cultures grew in 29/36 and 5/6(83%) with a metronidazole resistant strain(MIC > 32) were cured. Conclusions: 1. The single TT capsule combined with omeprazole is well tolerated with minimal adverse effects. 2. The regimen can achieve 92% cure rate(PP) and these results agree with previous reports where Quadruple Therapy was used with the 4 drugs given separately. 3. This new T r capsule packages bismuth triple and quadruple therapy into an attractive first line mono- or dual-therapy. Sneculation: When a PPI is added into this TT capsule we may finally be approaching the affordable, efficacious, tolerable, oneweek monotherapy 'silver bullet' to treat H. pylori infection.
GASTROENTEROLOGY Vol. 114, No. 4
G0398 INFLUENCE OF PANTOPRAZOLE 40 M G AND OMEPRAZOLE 20 MG ON MEAL-STIMULATED GASTRIC ACID SECRETION. H.G. Dammann, F. Burkhardt, Institute for Clinical Research, Hamburg, FRG. Purpose: The aim of this double-blind, placebo-controlled, three-fold cross-over study was to investigate, by means of meal-stimulated acid secretion, the extent to which differences in plasma half-life, bioavailability and the recommended therapeutic dose can influence the antisecretory potency of pantoprazole (P) and omeprazole (O). Methods: 12 healthy male volunteers (age: 24-35 years) received pantoprazole 40 mg, omeprazole 20 mg or placebo for five consecutive days. The individual treatment periods were separated by a 14 day washout phase. Meal stimulated acid-secretion was measured 24 hours after drug intake on day 1 and 4 hours after drug intake on days 3 and 5 of each treatment period. The pH of a standardized test meal (600 ml) was adjusted to 5 and the meal was infused into the stomach within 5 min. Thereafter the meal was aspirated continuously over 2 hours titrated with 0.1 n NaOH to pH 5 and then reinfused into the stomach. Results: Acid secretion (mmol H+/2h) is summarized in the following table: Day
Placebo
1
21.3)6.8
Pantoprazole 40 nag I1.1)8.1
Omelarazole 2Omg 15.3)8.8
3
26.2 ) 6,9
3.3 ) 3.8
8.5 ) 8.8
5
23.0 ) 6.4
3.5 ) 4.0
6.9 ) 8.9
p < 0.05 sign rank test (two sided, per protocol) On day 1 only P 40 mg was statistically superior to placebo (p < 0.05). On days 3 and 5 both proton pump inhibitors were superior to placebo (p < 0.05), and on days 1 and 3 P 40 mg was superior to 0 20 mg (p < 0.05). Conclusion: This investigation shows a significantly more rapid onset of action and a significantly higher antisecretory potency of pantoprazole compared to omeprazole. • G0399 CELLULAR ORIGIN OF BARRETT'S EPITHELIUM: A CRITICAL ANALYSIS USING A NOVEL BIOMARKER. K.M, Das, N Botros, PS Amenta. UMDNJ-Robert Wood Johnson Medical School and Robert Wood Johnson University Hospital, New Brunswick, NJ. mAb DAS-1 (previously called 7E12H12), is a murine monoclonai antibody (IgM isotype) developed against a colon epithelial glycoprotein (CEP) that reacts specifically with normal colon epithelium, but not with the mucosa from 17 other organs including esophagus, gastroesophageal junction (GEJ), cardia and the rest of stomach and small intestine (J Immunol 1987; 139:77). However, it does react sensitively with Barrett's epithelium (BE) and adenocarcinoma of the esophagus arising from BE (Ann Int Med 1994; 120:753). The cellular origin of BE is unknown. AIM and METHODS: Using this novel mAb, we examined the immunoreactivity of the distal esophagus including the submucosal glands by a sensitive immunoperoxidase assay (IPA). Seventeen surgical specimens of distal esophagus, including GEJ (histologically normal segments), 5 salivary glands (both parotid and minor salivary glands), 3 full thickness gastric mucosa, and 3 duodenal biopsy specimens containing Brunner's glands were analyzed. Only histologically normal areas were selected. In addition to the IPA, serial sections of these specimens were also examined by routine H&E and with alcian blue high iron diamine, pH 2.5 (AB/HID). Three samples of histologically proven BE, with specialized columnar epithelium, were examined in parallel with each experiment as positive control. An unrelated murine MOPC-IgM was used as a negative control. RESULTS: mAb DAS-I stained strongly a small number of glandular epithelial cells in the submucosal glands in the distal esophagus/GEL The staining was intense and was also clearly evident in the ductai epithelium of these glands. However, overlying luminal squamous epithelium or normal GE junctional epithelium and cardia did not react with mAb DAS-1. Each of the 3 BE specimens clearly reacted with the rnAb. mAb DAS-1 did not show any reactivity in the glandular epithelium in any of the salivary glands, gastric and Brunner's glands. However, AB/HID staining was positive in all cells of the esophageal submucosal glands, as well as in the salivary and gastric glands. CONCLUSION: These data indicate phenotypic similarity of BE with specific cells in the submucosal glands/ducts of the distal esophagus/GEJ, suggesting the latter as a potential source of origin of BE. G0400 ULTRA-SHORT COURSE THERAPY FOR ERADICATION OF HELICO. BACTER PYLORI. Jonathan David, M.D., FACP, FACG, Magdi Khalil, M.D., Ben Ten'any, M.D., Lisa A. Ozick, M.D., FACG Columbia University College of Physicians and Surgeons, Harlem Hospital Center, New York, NY Introduction: Standard protocols for eradication of Helicobacter pylori (Hp) require a 14 day course of antibiotics. Certain 7 day drug regimens recently have been shown to be effective, but there has been little published about eradication regimens shorter than 7 days. Aim; To investigate the efficacy and tolerability of an Hp eradication regimen given for 3 or 5 days. Methods: Patients were eligible if they had either a gastric or duodenal ulcer on endoscopy, and Hp found on rapid urease testing and pathology. They
were then randomly assigned (in a 2:2:1 fashion) to either a 3, 5, or 7 day course of quadruple therapy with: omeprazole 40 mg bid, PeptoBismol tablets 2 po qid, tetracycline 500 mg qid, and clarithromycin 500 mg tid. Additional omeprazole 20 mg qd was then given to complete a 4 week course. Follow up endoscopy was done at least 4 weeks after completion of the omeprazole. Successful eradication was defined as a negative rapid urease of biopsies taken from both the antrum and fundus and placed in the same well. The rapid urease tests were read by blinded investigators. Results: Eradication rates were as follows: 3 day ann: 9 of 10 subjects (90%); 5 day arm: 10 of 11 subjects (91%); 7 day arm: 3 of 3 subjects (100%; p=NS vs. 3 day and 5 day groups). All subjects completed their antibiotics without ill effects, but the patient in the 5 day arm who failed eradication did not take omeprazole after the initial 5 day quadruple therapy. Conclusions: This small, preliminary study suggests that "ultra-short course" quadruple therapy for Hp eradication is well tolerated, and that it may be as effective as many accepted regimens of 7 or even 14 days. More research is needed in this area. G0401
HELICOBACTER PYLORI RESISTANCE TO CLARITHROMYCIN, METRONIDAZOLE, AMOXICILLIN, TETRACYCLIN, AND TROVAFLOXACIN I N THE NETHERLANDS. Y.J. Debets-Ossenkopp, A.J. Herscbeid, E.J. Kuipers, J.G. Kusters, C.M.J.E. Vandenbroucke-Grauls. Dept. of Medical Microbiology en Gastroenterology. University Hospital "Vrije Universiteit" P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Clarithromycin and metronidazole are most active in the treatment of infections with 11. pylori and hence frequently used. Successful treatment is becoming more and more compromised by emerging resistance against these two antibiotics. The neomacrolides clarithromycin, azithromycin and roxitromycin have been introduced recently and are used increasingly in the Netherlands. In this study we determined the prevalence of primary antibiotic resistance of H. pylori in the Netherlands. Trovafioxacin is not yet approved for treatment of H. pylori infections but was included in the study because this new quinolone appears a promising candidate for the treatment of H. pylori infections. Clarithromycin, metronidazole, tetracyclin, and amoxicillin were studied, because of their proven value. Methods H. pylori isolates were collected from 18 different medical microbiology laboratories throughout the Netherlands. Each laboratory forwarded between 15 and 20 consecutive isolates from patients presenting for endoscopy between August and November 1997. MIC's for all antibiotics were determined by the E-test. Results: The resistance rate to clarithromycin was low, between 1 and 3% (MIC < 2 mg/L). Resistance rates for metronidazole were as high as 30% (MIC > 32 rag/L). None of the isolates was resistant to tetracyclin or amoxiciUin (all MIC's lower than 2 mg/L and 0.032 mg/L respectively). Breakpoints for trovafloxacin are not available yet, but the MIC's of the isolates varied between 0.016 and 3 mg/L. Con~lusi0n: In the Netherlands, only resistance to metronidazole in H. pylori has reached significant levels. The resistance rate to clarithromycin remains low, while it is non-existent for ampoxicilin and tetracyclin. Trovafloxacin appears a promising agent. G0402
TOWARDS MONOTHERAPY FOR HELICOBACTER PYLORI INFECTION: FIRST RESULTS WITH A SINGLE TRIPLE CAPSULE. de Boer WA, Borody TL Sint Anna Hospital, Oss, The Netherlands and Centre for Digestive Diseases, Sydney, NSW 2046, Australia Two week bismuth triple therapy(Tr) is the oldest effective and most investigated anti-H, pylori therapy. Treatment duration can be reduced to 7 days if a proton pump inhibitor (PPI) is added (Quadruple Therapy) resulting in the highest known cure-rates, usually above 95%. However, patients need to take numerous pills per day and the regimen is perceived as complex. Fear of non-compliance may have delayed its acceptance. Recently an "all in one" triple capsule has became available containing per 2 capsules 108mg of bismuth subcitrate, 500mg of tetracycline HC1 and 250mg of metronidazole. We report on the tolerability and efficacy of this new patient-friendly formulation of bismuth TT. Methods: In an open, two-centre study, consecutive infected patients with ulcer disease or non-ulcer dyspepsia were treated with omeprazole 20mg bd and the 'single triple' 2 capsules qid day 17. H. pylori status was determined before and at least 4 weeks after therapy by endoscopy with at least 3 antral and 2 corpus biopsies for CLO-test, histology and culture. An E-test was used for the antibiogram. Results: 37(19F/18M) patients were included and complete compliance was achieved in 36/37(97%). Tolerability was excellent with one 'drop out' due to allergy with 87% reporting absence of adverse effects. Patients expressed no problems with the size or the number of capsules(10/d). Over-all 33/36 (92%), were cured per protocol(PP) and 33/37(89%) intention to treat. Cultures grew in 29/36 and 5/6(83%) with a metronidazole resistant strain(MIC > 32) were cured. Conclusions: 1. The single TT capsule combined with omeprazole is well tolerated with minimal adverse effects. 2. The regimen can achieve 92% cure rate(PP) and these results agree with previous reports where Quadruple Therapy was used with the 4 drugs given separately. 3. This new T r capsule packages bismuth triple and quadruple therapy into an attractive first line mono- or dual-therapy. Sneculation: When a PPI is added into this TT capsule we may finally be approaching the affordable, efficacious, tolerable, oneweek monotherapy 'silver bullet' to treat H. pylori infection.