A1304 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
5952 PANTOPRAZOLE LACKS INTERACTION WITH THE NSAID NAPROXEN.
infection has a major impact on the relapse rate of GERD. Eradication therapy for H. pylori prolongs the disease free interval in GERD patients.
H.-V. Schulz, M. Hartmann, S. Krupp, M. Schuerer, R. Huber, R. Luehmann, Th. Bethke, W. Wurst, Lafaa, Bad Schwartau, Germany; Byk Gulden, Konstanz, Germany.
Cox-Regression Prediction c o '-E 1.0r-....~-~-~-~~~.....-~_~~--.
Introduction: Treatment with non steroidal antiinflammatory drugs (NSAIDs) increases the risk of developing gastrointestinal ulcers. For prophylaxis or treatment of such lesions, antisecretory drugs are used. Pantoprazole is a potent H+/K+-ATPase inhibitor with a low potential to interact with the cytochrome P450 enzyme system. In particular, lack-ofinteraction with CYP2C9, the subenzyme mainly responsible for metabolizing most of the NSAIDs, (e.g. diclofenac) has been shown. However, as pantoprazole and NSAIDs may be frequently administered concomitantly a further interaction study was performed. Methods: 24 healthy male subjects (age 18 - 41 years, weight 65 - 89 kg) were enrolled and completed the study. They underwent three treatment periods of 7 days each in a randomized order: • pantoprazole 40 mg sid, • naproxen 250 mg bid, • pantoprazole 40 mg sid + naproxen 250 mg bid. Blood was frequently withdrawn on day 7 of each period for pharmacokinetic analysis. AVC and C m ,,, were calculated during steady state. Lack-of-interaction was evaluated using the bioequivalence approach. Results: Pharmacokinetic results see table. All treatments were well tolerated. There were no clinically relevant changes in vital signs, ECG or clinical laboratory. Conclusion: The 90% CIs for the respective AVC and C m ax ratios were well within 0.8 - 1.25, the accepted range for bioequivalence. Thus, pantoprazole does not affect the serum concentrations of naproxen, so that both drugs can be safely administered concomitantly.
o '- 08 a. 0.7
Pharmacokinetic results Equivalence ratio (Test/Reference) Point estimate
Reference: geom. mean (N=24) (68% range)
Test: geom. mean (N=24) (68% range)
Naproxen without pantoprazole
Naproxen with pantoprazole
1.00 (0.96, 1.04)
66.1 (55.6, 78.7)
Pharmacokinetic characteristics of naproxen
o 0.9 0-
0.3 -Control > 0.2 Eradicated ',0:; 0.1 - - - Hp-Posilive ..!!! 0.0 t...etI
Days after end of treatment
5954 IS THERE REALLY A RISK OF GASTRO-ESOPHAGEAL REFLUX DISEASE AFTER H. PYLORI - ERADICATION - THERAPY? Rodolfo Ea Seelis, Werner Dohmen, Practice for Gastroenterology, Aachen, Germany; Practice for Gen Medicine, Aachen, Germany. Recently the influence of H.pylori (Hp) eradication on gastro - esophageal reflux disease (GERD) has become a major focus of attention; however, data currently available are conflicting. The primary objective of our retrospective, community based study therefore was to investigate the effect of Hp-eradication on both, the incidence of GERD symptoms and the development of esophagitis (ESOP). 308 general practice patients (age 49.7 :!: 13.1 years; male 1 female = 57 % 143 %) with recurrent gastritis or ulcer disease, who had been treated for their Hp-infection were interviewed and reinvestigated (gastroscopy, urease-test, histology) 2 to 57 months after Hp-eradication (Hp-X). Around 1/4 of all patients initially reported GERD symptoms prior to Hp-eradication, Of these patients 1/3 with successful Hp-treatment experienced improvement of their reflux symptoms, while no change of symptoms was seen in patients with persistent Hp-infection. Of the patients initially lacking GERD symptoms as few as 5.5 % reported reflux symptoms after successful Hp-eradication and only 1.6 % of the patients developed esophagitis. However, none of the patients suffering from ulcer disease (n = 112) experienced reflux symptoms or esophagitis after eradication. In conclusion, our study did not reveal an increased risk of initiating GERD after successful Hp-eradication, even not in patients with ulcer disease.
5953 DOES ERADICATION OF HELICOBACTER PYLORI ALTER GASTROESOPHAGEAL REFLUX DISEASE (GERD)?
Werner Schwizer, Miriam Thumshim, Irene Guldenschuh, Dieter Menne, Michael Fried, Gastroenterology, Univ Hosp, Zurich, Switzerland; Biomed Software, Tubingen, Germany. Current data are conflicting whether Hp eradication increases or reduces the risk for GERD. Aim: To investigate tiIe effect of Hp eradication on esophageal pH and GERD relapse. Methods: In a double blind, placebo controlled study 70 pts with GERD were randomized to 3 treatment groups according to their Hp status. All pts received lansoprazole (Lan) 30mg bid for 10 d followed by 30 mg Lan for 8 weeks. Hp+ve pts received either clarithromycine 500mg bid + amoxicilline 1000mg bid or placebo in the first 10 d. Hp-ve pts served as controls. Follow-up was made for 6 months at 2-week intervals using a standardized questionnaire. At study end or at relapse the initial investigations were repeated (endoscopy, esophageal I gastric 24h pH-metry, Hp serology, histology, breath test). Statistical analysis were made by Cox regression. Results: 58170 pts completed the study: a) Hp+ve group, n=16; b)Hp-ve eradicated pts (ERA), n=13; c)Hp-ve controls, n=29. Relapse was faster (p=0.046)in Hp+ve pts (54 d) vs. Hp-ve ERA (100 d) and faster (p=0.018) vs. controls (110 d). Relapse rates correlated with the grade of esophagitis at study entry (p=0.016). Relapse was lowest for pts without esophagitis (127 d) and highest for pts with esophagitis lIIIlY (18 d). Hp+ve pts relapsed faster (p=0.049)compared to Hp-ve ERA and faster compared to controls (p=0.014) when corrected for the esophagitis grade. Conclusion: Hp
GERD afterHp·X GERD priorto, but notafterHp·X GERD priorto andafterHp·X ESOP afterHp·X ESOP priorto, but not afterHp·X ESOP priorto andafterHp·X
successful Hp·X n =254(100 %)
unsuccessful Hp·X n = 54(100%j
n = 14(5.5 %) n=22(8.7%) n=3.4(13.4%) n = 4 (1.6 %) n = 4 (1.6 %) n = 10(3.9 %)
n = 0 (0%) n = 0 (0%) n = 14(25.9 %) n = 2 (3.7 %) n = 0 (0 %) n = 4 (7.4%)
5955 SCHATZKI'S RINGS ARE STRONGLY ASSOCIATED WITH HIATAL HERNIA AND GASTROESOPHAGEAL REFLUX DISEASE. Randy Shahbazian, David J. Bowrey, Cedric G. Bremner, Reginald Y. Lord, Peter F. Crookes, James E. Huprich, Dennis Blorn, Jeffrey H. Peters, Steven R. DeMeester, Michael G. Wood, Anna Kaminski, Tom R. DeMeester, Univ of Southern CA, Los Angeles, CA. Aim: To clarify the pathogenesis and clinical features of Schatzki s rings using a large series of intensively studied patients. Methods: 71 (60% male) patients with either an endoscopic or barium contrast radiologic diagnosis of Schatzki s ring were investigated at this institution between 1992-1999. Endoscopic criteria for diagnosis were the presence of a soft mucosal ring at the squamocolumnar junction and the ability to pass an endoscope through the ring. A radiological diagnosis required the presence of a short symmetrical concentric narrowing. Tighter, longer, or asymmetrical narrowings were classified as strictures and were excluded. Patients in whom drug ingestion might have contributed to the formation of a luminal narrowing were excluded. Results: The commonest symptoms were heartburn (94%) and regurgitation (88%). 72% complained of dysphagia, but in only 145 was this the presenting complaint. Increased distal esophageal acid exposure was present on 24 hour pH monitoring in 69% of patients but there was a lower prevalence of either histologic (28%) or endoscopic (24%) esophagitis. Manometric criteria indicating mechanical incompetence of the lower esophageal sphincter were present in 59%. A hiatal hernia was present in 97%. There were no significant differences between the motility findings in patients with dysphagia compared with those