Acid suppression therapy: Where do we go from here?

Digestive Diseases

Volumn 24, Issue 1-2, 2006, Pages 11-46

  Scarpignato, Carmelo ^a   Pelosini, Iva ^a   Di Mario, Francesco ^a  

^a UNIVERSITY OF PARMA   (Italy)

Author keywords

Acid inhibition; Antisecretory drugs; CCK 2 receptor antagonists; Ebrotidine; Gastric acid secretion; H 2 receptor antagonists; Ilaprazole Tenatoprazole; Lafutidine; Potassium competitive acid blockers; Proton pump inhibitors

Indexed keywords

1 (2,3 DIHYDRO 1 METHYL 2 OXO 5 PHENYL 1H 1,4 BENZODIAZEPIN 3 YL) 3 (3 METHYLPHENYL)UREA; 1 [2,3 DIHYDRO 1 (2' METHYLPHENACYL) 2 OXO 5 PHENYL 1H 1,4 BENZODIAZEPIN 3 YL] 3 (3 METHYLPHENYL)UREA; 1 [2,3 DIHYDRO 2 OXO 1 PIVALOYLMETHYL 5 (2 PYRIDYL) 1H 1,4 BENZODIAZEPIN 3 YL] 3 [3 (METHYLAMINO)PHENYL]UREA; 1 [5 (3 AZABICYCLO[3.2.2]NON 3 YL) 2,3 DIHYDRO 1 METHYL 2 OXO 1H 1,4 BENZODIAZEPIN 3 YL] 3 (3 METHYLPHENYL)UREA; 4 [3 (1,3 BENZODIOXOL 5 YL)THIOUREIDO] N [3 [3 (PIPERIDINOMETHYL)PHENOXY]PROPYL]BUTYRAMIDE; 7 (4 FLUOROBENZYLOXY) 2,3 DIMETHYL 1 [(2 METHYLCYCLOPROPYL)METHYL] 1H PYRROLO[2,3 D]PYRIDAZINE; 8 [(2,6 DIMETHYLBENZYL)AMINO] N (2 HYDROXYETHYL) 2,3 DIMETHYLIMIDAZOL[1,2 A]PYRIDINE 6 CARBOXAMIDE; 8 BENZYLOXY 2 METHYLIMIDAZO[1,2 A]PYRIDINE 3 ACETONITRILE; AMOXICILLIN; ANTIBIOTIC AGENT; AZD 0865; BENATOPRAZOLE; BICARBONATE; BOMBESIN[6-13][6 DEXTRO PENTAFLUOROPHENYLALANINE 11 DEXTRO ALANINE] METHYL ESTER; BW 2258U89; BY 841; CHOLECYSTOKININ B RECEPTOR ANTAGONIST; CIMETIDINE; CLARITHROMYCIN; CP 66948; CR 02194; CS 526; EBROTIDINE; ESOMEPRAZOLE; GASTRIMMUNE; HISTAMINE H3 RECEPTOR ANTAGONIST; ILAPRAZOLE; INSEGIA; ITRIGLUMIDE; L 368935; LAFUTIDINE; LANSOPRAZOLE; LEMINOPRAZOLE; METRONIDAZOLE; NONSTEROID ANTIINFLAMMATORY AGENT; OMEPRAZOLE; OX 17; PANTOPRAZOLE; POTASSIUM COMPETITIVE ACID BLOCKER; PROTON PUMP INHIBITOR; PUMAPRAZOLE; R 105266; RABEPRAZOLE; RANITIDINE; REVAPRAZAN; SORAPRAZAN; STOMACH SECRETION INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; Z 360;

ACIDITY; CLINICAL TRIAL; DIGESTIVE SYSTEM INJURY; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; ELECTIVE SURGERY; ERADICATION THERAPY; GASTRODUODENAL ULCER; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL HEMORRHAGE; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HUMAN; MUCOSAL BLEEDING; NONHUMAN; PATIENT DECISION MAKING; PEPTIC ULCER; PEPTIC ULCER BLEEDING; PRIORITY JOURNAL; REVIEW; STOMACH ACID SECRETION; STOMACH DISEASE; STOMACH PH; STRESS; SYMPTOMATOLOGY; ULCER HEALING; ZOLLINGER ELLISON SYNDROME;

ANTI-ULCER AGENTS; ENZYME INHIBITORS; GASTRIC ACID; GASTROESOPHAGEAL REFLUX; HISTAMINE H2 ANTAGONISTS; HUMANS; PROTON PUMPS; TREATMENT OUTCOME;

EID: 33646732206     PISSN: 02572753     EISSN: None     Source Type: Journal    
DOI: 10.1159/000091298     Document Type: Review

References (308)

1. Hersey SJ, Sachs G: Gastric acid secretion. Physiol Rev 1995;75:155-189.
2. Aihara T, Nakamura E, Amagase K, Tomita K, Fujishita T, Furutani K, Okabe S: Pharmacological control of gastric acid secretion for the treatment of acid-related peptic disease: past, present, and future. Pharmacol Ther 2003;98:109-127.
3. Lindstrom E, Chen D, Norlen P, Andersson K, Hakanson R: Control of gastric acid secretion: the gastrin-ECL cell-parietal cell axis. Comp Biochem Physiol A Mol Integr Physiol 2001;128:505-514.
4. Makhlouf GM, Schubert ML: Gastric somatostatin: a paracrine regulator of acid secretion. Metabolism 1990;39(suppl 2):138-142.
5. Chey WY, Chang TM: Neural control of the release and action of secretin. J Physiol Pharmacol 2003;54(suppl 4):105-112.
6. Olbe L, Carlsson E, Lindberg P: A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov 2003;2:132-139.
7. Stedman CAM, Barclay ML: Comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther 2000;14:963-978.
8. Sachs G: Proton pump inhibitors and acid-related diseases. Pharmacotherapy 1997;17:22-37.
9. Kromer W: Relative efficacies of gastric proton-pump inhibitors on a milligram basis: desired and undesired SH reactions. Impact of chirality. Scand J Gastroenterol 2001;36(suppl 234):3-9.
10. +-ATPaSe. Annu Rev Pharmacol Toxicol 1995;35:277-305.
11. Wolfe MM, Sachs G: Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology 2000;118(suppl 1):S9-S31.
12. 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.
13. Poynard T, Lemaire M, Agostini H: Metaanalysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. Eur J Gastroenterol Hepatol 1995;7:661-665.
14. Salas M, Ward A, Caro J: Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials. BMC Gastroenterol 2002;2:17-23.
15. Scarpignato C, Pelosini I: Antisecretory drugs for eradication of Helicobacter pylori: antibacterial activity and synergism with antimicrobial agents. Progr Basic Clin Pharmacol 1999;11:136-180.
16. Gisbert JP, Gonzalez L, Calvet X, Roque M, Gabriel R, Pajares JM: Proton pump inhibitor, clarithromycin and either amoxicillin or nitro-imidazole: a meta-analysis of eradication of Helicobacter pylori. Aliment Pharmacol Ther 2000;14:1319-1328.
17. Vallve M, Vergara M, Gisbert JP, Calvet X: Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis. Aliment Pharmacol Ther 2002;16:1149-1156.
18. Malfertheiner P, Mégraud F, O'Morain C, Hungin APS, Jones R, Axon A, Graham DY, Tytgat G, the European Helicobacter pylori Study Group (EHPSG): Current concepts in the management of Helicobacter pylori infection - the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther 2002;16:167-180.
19. Malfertheiner P, Mégraud F, O'Morain C: Guidelines for the management of Helicobacter pylori infection - summary of the Maastricht-3 2005 Consensus Report. Eur Gastroenterol Rev 2005, pp 59-62 [http://www. touchbriefings.com/cdps/cditem.cfm?nid= 1489]
20. Marshall BJ, Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;i:1311-1315.
21. Marshall BJ: The 1995 Albert Lasker Medical Research Award. Helicobacter pylori. The etiologic agent for peptic ulcer. JAMA 1995;274:1064-1066.
22. Tytgat GNJ, Noach LA, Rauws EAJ: Helicobacter pylori infection and duodenal ulcer disease. Gastroenterol Clin North Am 1993;22:127-139.
23. Leodolter A, Kulig M, Brasch H, Meyer-Sabellek W, Willich SN, Malfertheiner P: A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer. Aliment Pharmacol Ther 2001;15:1949-1958.
24. Ford AC, Delaney BC, Forman D, Moayyedi P: Eradication therapy in Helicobacter pylori-positive peptic ulcer disease: systematic review and economic analysis. Am J Gastroenterol 2004;99:1833-1855.
25. Bazzoli F, BianchiPorro G, Bianchi MG, Molteni M, Pazzato P, Zagari RM: Treatment of Helicobacter pylori infection. Indications and regimens: an update. Dig Liver Dis 2002;34:70-83.
26. Gisbert JP, Pajares JM: Systematic review and meta-analysis: is one-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer? Aliment Pharmacol Ther 2005;21:795-804.
27. Metz DC, Pisegna JR, Fishbeyn VA, Benya RV, Jensen RT: Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. World J Surg 1993;17:468-480.
28. Metz DC, Jensen RT: Advances in gastric antisecretory therapy in Zollinger-Ellison. Front Gastrointest Res 1995;23:240-257.
29. 2-antagonist refractory ulcers. Digestion 1989;44(suppl 1):31-39.
30. Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH: Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion 1992;51(suppl 1):59-67.
31. Bell NJ, Hunt RH: Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease. Gut 1992;33:118-124.
32. Chiba N, De Gara CJ, Wilkinson JM, Hunt RH: Speed of healing and symptom relief in grade II-IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997;112:1798-1810.
33. 2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease (Cochrane Review). Cochrane Database Syst Rev 2004;4:CD002095.
34. Scarpignato C, Pelosini I: Prevention and treatment of non-steroidal anti-inflammatory drug-induced gastro-duodenal damage: rationale for the use of antisecretory compounds. Ital J Gastroenterol Hepatol 1999;31(suppl 1):S63-S72.
35. Koch M, Dezi A, Ferrario F, Capurso I: Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996;156:2321-2332.
36. Leandro G, Pilotto A, Franceschi M, Bertin T, Lichino E, Di Mario F: Prevention of acute NSAID-related gastroduodenal damage: a meta-analysis of controlled clinical trials. Dig Dis Sci 2001;46:1924-1936.
37. Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, McGowan J: Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002;4:CD002296.
38. Hooper L, Brown TJ, Elliott R, Payne K, Roberts C, Symmons D: The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004;329:948.
39. Berstad A: Does profound acid inhibition improve haemostasis in peptic ulcer bleeding? Scand J Gastroenterol 1997;32:396-398.
40. Geun WP: Are there indications for intravenous acid inhibition in the prevention and treatment of upper GI bleeding? Scand J Gastroenterol 2000:35(suppl 232):10-20.
41. Zed PJ, Loewen PS, Slavik RS, Marra CA: Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers. Ann Pharmacother 2001;35:1528-1534.
42. 2-antagonists: a meta-analysis of their efficacy in treating bleeding peptic ulcer. Aliment Pharmacol Ther 2001;15:917-926.
43. 2-receptor antagonists in bleeding peptic ulcer. Aliment Pharmacol Ther 2002;16:1137-1142.
44. Selby NM, Kubba AK, Hawkey CJ: Acid suppression in peptic ulcer haemorrhage: a 'meta-analysis'. Aliment Pharmacol Ther 2000;14:1119-1126.
45. Leontiadis GI, Sharma VK, Howden CW: Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ 2005;330:568.
46. Leontiadis GI, Sharma VK, Howden CW: Systematic review and meta-analysis: proton-pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay - results from the Cochrane Collaboration. Aliment Pharmacol Ther 2005;22:169-174.
47. Bardou M, Toubouti Y, Benhaberou-Brun D, Rahme E, Barkun AN: Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding. Aliment Pharmacol Ther 2005;21:677-686.
48. Khuroo MS, Khuroo MS, Farahat KL, Kagevi IE: Treatment with proton pump inhibitors in acute non-variceal upper gastrointestinal bleeding: a meta-analysis. J Gastroenterol Hepatol 2005;20:11-25.
49. Leontiadis GI, Sharma VK, Howden CW: Systematic review and meta-analysis: enhanced efficacy of proton-pump inhibitor therapy for peptic ulcer bleeding in Asia - a post-hoc analysis from the Cochrane Collaboration. Aliment Pharmacol Ther 2005;21:1055-1061.
50. Chong E, Ensom MH: Pharmacogenetics of the proton pump inhibitors: a systematic review. Pharmacotherapy 2003;23:460-471.
51. Furuta T, Shirai N, Sugimoto M, Ohashi K, Ishizaki T: Pharmacogenomics of proton pump inhibitors. Pharmacogenomics 2004;5:181-202.
52. Andriulli A, Annese V, Caruso N, Pilotto A, Accadia L, Niro AG, Quitadamo M, Merla A, Fiorella S, Leandro G: Proton-pump inhibitors and outcome of endoscopic hemostasis in bleeding peptic ulcers: a series of meta-analyses. Am J Gastroenterol 2005;100:207-219.
53. Gisbert J, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Munoz J: H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Cochrane Database Syst Rev 2003;4:CD004062.
54. 2-receptor antagonists in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1995;9(suppl 1):9-14.
55. 2 de l'histamine. Gastroenterol Clin Biol 1999;23:S78-S89.
56. 2-receptor antagonists. An overview. Scand J Gastroenterol 1992;27(suppl 193):14-19.
57. Sandvik AK, Brenna E, Waldum HL: Review article: the pharmacological inhibition of gastric acid secretion: tolerance and rebound. Aliment Pharmacol Ther 1997;11:1013-1018.
58. Scarpignato C: Antisecretory drugs, Helicobacter pylori infection and symptom relief in GORD: still an unexplored triangle. Dig Liver Dis 2005;37:468-474.
59. 2- receptor antagonists in the treatment of functional (nonulcer) dyspepsia: a meta-analysis of randomized controlled clinical trials. Aliment Pharmacol Ther 2000;15:1291-1299.
60. 2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients. Aliment Pharmacol Ther 2005;21:1299-1312.
61. Earnest D, Robinson M, Rodriguez-Stanley S, Ciociola AA, Jaffe P, Silver MT, Kleoudis CS, Murdock RH: Managing heartburn at the 'base' of the GERD 'iceberg': effervescent ranitidine 150 mg b.d. provides faster and better heartburn relief than antacids. Aliment Pharmacol Ther 2000;14:911-918.
62. Robinson M, Rodriguez-Stanley S, Ciociola AA, Filinto J, Zubaidi S, Miner PB Jr, Gardner JD: Synergy between low-dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal-induced heartburn. Aliment Pharmacol Ther 2001;15:1365-1374.
63. Peghini PL, Katz PO, Bracy NA, Castell DO: Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors. Am J Gastroenterol 1998;9:763-767.
64. 2 blockers improve nocturnal gastric acid control in GERD patients on proton pump inhibitors. Aliment Pharmacol Ther 2001;15:1351-1356.
65. 2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology 2002;122:625-632.
66. Cross LB, Justice LN: Combination drug therapy for gastroesophageal reflux disease. Ann Pharmacother 2002;36:912-916.
67. 2-receptor antagonist for the control of nocturnal gastric acid breakthrough. Cochrane Database Syst Rev 2004;4:CD004275.
68. Guda N, Mueller R, Vakil N: The effect of over-the-counter ranitidine (75 mg) on night-time heartburn in patients with erosive esophagitis on daily proton pump inhibitor maintenance therapy. Gastroenterology 2003;124:539A.
69. Orr WC: Night-time gastro-oesophageal reflux disease: prevalence, hazards, and management. Eur J Gastroenterol Hepatol 2005;17:113-120.
70. Tutuian R, Katz PO, Castell DO: Nocturnal acid breakthrough: pH, drugs and bugs. Eur J Gastroenterol Hepatol 2004;16:441-443.
71. Rackoff A, Agrawal A, Hila A, Mainie I, Tutuian R, Castell DO: Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy. Dis Esophagus 2005;18:370-373.
72. Katz PO, Tutuian R: Histamine receptor antagonists, proton pump inhibitors and their combination in the treatment of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol 2001;15:371-384.
73. McColl KEL, Kennerley P: Proton pump inhibitors - differences emerge in the hepatic metabolism. Digest Liver Dis 2002;34:461-467.
74. Thomson ABR: Are the orally administered proton pump inhibitors equivalent? A comparison of lansoprazole, omeprazole, pantoprazole, and rabeprazole. Curr Gastroenterol Rep 2000;2:482-493.
75. Langman MJS: Which PPI? Gut 2001;49:309-310.
76. Kromer W, Horbach S, Lühmann R: Relative efficacies of gastric proton pump inhibitors: their clinical and pharmacological basis. Pharmacology 1999;59:57-77.
77. Guidance on the use of proton pump inhibitors in the treatment of dyspepsia: NICE, UK: Technology Appraisal Guidance No 7, 2000 [http://www.NICE.org.uk]
78. Bardhan KD: Is there any acid peptic disease that is refractory to proton pump inhibitors? Aliment Pharmacol Ther 1993;7(suppl 1):13-31.
79. Amin MR, Postma GN, Johnson P, Digges N, Koufman JA: Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux. Otolaryngol Head Neck Surg 2000;125:374-378.
80. Sontag SJ: Persistent gastroesophageal reflux disease symptoms on standard proton-pump inhibitor therapy. Gastroenterol Clin North Am 2002;31(suppl 4):S77-S84.
81. Galmiche JP, Sacher-Huvelin S: Reflux gastro-œsophagien résistant aux inhibiteurs de la pompe à protons. Hépato-Gastro 2002;9:159-163.
82. Ashida K, Sakaguchi M, Tanaka M, Takiuchi H, Egashira Y, Katsu K: Clinical study on the pathophysiology and treatment of PPI-resistant ulcers. J Clin Gastroenterol 1995;20(suppl 2):S67-S71.
83. Katz PO: Lessons learned from intragastric pH monitoring. J Clin Gastroenterol 2001;33:107-113.
84. Hatlebakk JG, Katz PO, Castell DO: Medical therapy. Management of the refractory patient. Gastroenterol Clin North Am 1999;28:847-860.
85. Leite L, Lambrecht N, Sachs G, Castell D, Lagerstrom P: Is omeprazole resistance due to mutations of cysteine 813 or 822 in the acid pump? Gastroenterology 1995;108:A147.
86. 2-receptor antagonists after omeprazole failure: report of two cases. Am J Gastroenterol 1995;90:1874-1877.
87. Huber R, Kohl B, Sachs G, Senn-Bilfinger J, Simon WA, Sturm E: Review article: the continuing development of proton pump inhibitors with particular reference to pantoprazole. Aliment Pharmacol Ther 1995;9:363-378.
88. Tytgat GN: Shortcomings of the first-generation proton pump inhibitors. Eur J Gastroenterol Hepatol 2001;13(suppl 1):S29-S33.
89. Robinson M: New-generation proton pump inhibitors: overcoming the limitations of early-generation agents. Eur J Gastroenterol Hepatol 2001;13(suppl 1):S43-S47.
90. Sachs G: Improving on PPI-based therapy of GORD. Eur J Gastroenterol Hepatol 2001;13(suppl 1):S35-S41.
91. Anonymus: Tenatoprazole. Benatoprazole, TU-199. Drugs RD 2002;3:276-277.
92. Tonini M, De Giorgio R, De Ponti F: Novel therapeutic strategies in acid-related disorders. Expert Opin Ther Patents 2003;13:639-649.
93. Andersson K, Carlsson E: Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases. Pharmacol Ther 2005;108:294-307.
94. Geibel JP: Role of potassium in acid secretion. World J Gastroenterol 2005;11:5259-5265.
95. Parsons ME, Garner A: Drug development in gastroenterology - the changing view of industry. Aliment Pharmacol Ther 1995;9:457-463.
96. Hassan-Alin M, Niazi M, Röhss K, Sthenoff H: Esomeprazole, the S-isomer of omeprazole, is optically stable in humans. Gastroenterology 2000;118(suppl 2):A1244-A1245.
97. The Nobel Foundation: Information for the public. The 2001 Nobel Prize in Chemistry [www.nobel.se/chemistry/laureates/2001/public.htlm].
98. Cotton H, Elebring T, Larsson M, Li L, Sörensen H, von Unge S: Asymmetric synthesis of esomeprazole. Tetrahedron Asymmetry 2000;11:3819-3825.
99. Del Nozal MJ, Toribio L, Bernai JL, Alonso C, Jimenez JJ: Chiral separation of omeprazole and several related benzimidazoles using supercritical fluid chromatography. J Sep Sci 2004;27:1023-1029.
100. Lough JW, Wainer I: Chirality in Natural and Applied Sciences. Oxford, Blackwell Publishing, 2002, pp 1-336.
101. Stern L: The lesson of thalidomide. Clin Pharmacol Ther 1973;14:660-661.
102. Richardson P, Hideshima T, Anderson K: Thalidomide: emerging role in cancer medicine. Annu Rev Med 2002;53:629-657.
103. Williams K, Lee E: Importance of drug enantiomers in clinical pharmacology. Drugs 1985;30:333-354.
104. Lam Y: Stereoselectivty: an issue of significant importance in clinical pharmacology. Pharmacotherapy 1988;8:147-157.
105. Hutt AJ, Tan SC: Drug chirality and its clinical significance. Drugs 1996;52(suppl 57):1-12.
106. Pifferi G, Perucca E: The cost-benefit ratio of enantiomeric drugs. Eur J Drug Metab Pharmacokinet 1995;20:15-25.
107. Eichelbaum M: Enantiomers: implications and complications in developmental pharmacology. Dev Pharmacol Ther 1992;18:131-134.
108. Lee EJ, Williams ICM: Chirality. Clinical pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet 1990;18:339-345.
109. Brocks DR, Jamali F: Stereochemical aspects of pharmacotherapy. Pharmacotherapy 1995;15:551-564.
110. Scott AK: Stereoisomers and drug toxicity. The value of single stereoisomer therapy. Drug Saf 1993;8:149-159.
111. Hsu WH: Toxicity and drug interactions of levamisole. J Am Vet Med Assoc 1980;176:1166-1169.
112. Marzo A, Cardace G, Arrigoni Martelli E: Enzymes in stereoselective pharmacokinetics of endogenous substances. Chirality 1992;4:247-251.
113. Erlandsson P, Isaksson R, Lorentzon P, Lindberg P: Resolution of the enantiomers of omeprazole and some of its analogues by liquid chromatography on a trisphenylcarbamoylcellulose-based stationary phase. The effect of the enantiomers of omeprazole on gastric glands. J Chromatogr 1990;532:305-319.
114. Eichelbaum M: Pharmacokinetic and pharmacodynamic consequences of stereoselective drug metabolism in man. Biochem Pharmacol 1988;37:93-96.
115. Tucker GT, Lennard MS: Enantiomer-specific pharmacokinetics. Pharmacol Ther 1990;45:309-329.
116. Andersson T: Pharmacokinetics, metabolism and interactions of acid pump inhibitors - focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokinet 1996;31:9-28.
117. Egan LJ, Murray JA: New perspectives in gastric acid suppression: genetic polymorphisms predict the efficacy of proton pump inhibitors. Dig Dis 2000;18:58-63.
118. Tybring G, Bottiger Y, Widen J, Bertilsson L: Enantioselective hydroxylation of omeprazole catalyzed by CYP2C19 in Swedish white subjects. Clin Pharmacol Ther 1997;62:129-137.
119. Äbelö A, Andersson TB, Bredberg U, Skanbergl, Weidolf L: Stereoselective metabolism by human liver CYP enzymes of a substituted benzimidazole. Drug Metab Dispos 2000;28:58-64.
120. Andersson T, Bredberg E, Sunzel M, Antonsson M, Weidolf L: Pharmacokinetics (PK) and effect on pentagastrin stimulated peak acid output of omeprazole and its two optical isomers, S-omeprazole/esomeprazole (E) and R-omeprazole. Gastroenterology 2000;118 (suppl 2):A1210.
121. Junghard O, Hassan-Alin M, Hasselgren G: The effect of the area under the plasma concentration vs. time curve and the maximum plasma concentration of esomeprazole on intragastric pH. Eur J Clin Pharmacol 2002;58:453-458.
122. Tonini M, Vigneri S, Savarino V, Scarpignato C: Clinical pharmacology and safety profile of esomeprazole, the first enantiomerically pure proton pump inhibitor. Dig Liver Dis 2001;33:600-606.
123. Vigneri S, Tonini M, Scarpignato C, Savarino V: Improving opportunities for effective management of gastro-esophageal reflux disease. Dig Liver Dis 2001;33:720-730.
124. Scott LJ, Dunn CJ, Mallarkey G, Sharpe M: Esomeprazole. A review of its use in the management of acid-related disorders. Drugs 2002;62:1503-1538.
125. Johnson DA: Review of esomeprazole in the treatment of acid disorders. Expert Opin Pharmacother 2003;4:253-264.
126. Kim KA, Shon JH, Park JY, Yoon YR, Kim MJ, Yun DH, Kim MK, Cha IJ, Hyun MH, Shin JG: Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19. Clin Pharmacol Ther 2002;72:90-99.
127. 450 enzymes. Drug Metab Dispos 2003;31:1227-1234.
128. Miura M, Tada H, Yasui-Furukori N, Uno T, Sugawara K, Tateishi T, Suzuki T: Effect of clarithromycin on the enantioselective disposition of lansoprazole in relation to CYP2C19 genotypes. Chirality 2005;17:338-344.
129. Tanaka M, Yamazaki H, Hakusui H, Nakamichi N, Sekino H: Differential stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor in extensive and poor metabolizers of pantoprazole - a preliminary study. Chirality 1997;9:17-21.
130. Cao H, Wang MW, Sun LX, Ikejima T, Hu ZQ, Zhao WH: Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid-related lesions and acid secretion in rats and guinea-pigs. J Pharm Pharmacol 2005;57:923-927.
131. Mano N, Oda Y, Takakuwa S, Chiku S, Nakata H, Asakawa N: Plasma direct injection high-performance liquid chromatographic method for simultaneously determining E3810 enantiomers and their metabolites by using flavoprotein-conjugated column. J Pharm Sci 1996;85:903-907.
132. TAP 2005 Press Release: TAP initiates phase III studies for investigational new gastroenterology product [http://www.tap.com/npr_2005_8_30. asp]
133. ClinicalTrials.gov. Ongoing Trials with TAK-390MR [http://www. clinicaltrials. gov/ct/search;jsessionid=A1CC1E29324CED0D3 E0263C6AD8B0243?term= TAK-390MR].
134. 450 forms by lansoprazole and omeprazole in vitro. Xenobiotica 2005;35:27-38.
135. Rettie AE, Jones JP: Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics. Annu Rev Pharmacol Toxicol 2005;45:477-494.
136. Andersson T: Single-isomer drugs. True therapeutic advances. Clin Pharmacokinet 2004;43:279-285.
137. Raghunath AS, Green JR, Edwards SJ: A review of the clinical and economic impact of using esomeprazole or lansoprazole for the treatment of erosive esophagitis. Clin Ther 2003;25:2088-2101.
138. Anonymous: Do single stereoisomer drugs provide value? Ther Initiative 2002;45 (June-Sept letter) [http://www.ti.ubc.ca/pages/letter45.htm]
139. Anonymous: Prilosec, Nexium and stereoisomers. Med Lett 2003;45:49-52.
140. Mansfield P, Henry D, Tonking A: Single-enantiomer drugs. Elegant science, disappointing results. Clin Pharmacokinet 2004;43:287-290.
141. Henry DA, Lexchin J: Medicines, health and commerce: a global perspective of the pharmaceutical industry: industry as medicine provider. Lancet 2002;360:1590-1595.
142. Bardhan KD, Williamson M, Royston C, Lyon C: Admission rates for peptic ulcer in the Trent region, UK, 1972-2000. Changing pattern, a changing disease? Dig Liver Dis 2004;36:577-588.
143. Fries JF, Murtagh KN, Bennett M, Zatarain E, Lingala B, Bruce B: The rise and decline of nonsteroidal anti-inflammatory drug-associated gastropathy in rheumatoid arthritis. Arthritis Rheum 2004;50:2433-2440.
144. Tytgat GN: Are there unmet needs in acid suppression? Best Pract Res Clin Gastroenterol 2004;18(suppl):67-72.
145. Hunt RH: The unmet needs in delayed-release proton-pump inhibitor therapy in 2005. Aliment Pharmacol Ther 2005;22(suppl 3):10-19.
146. Pezanoski J, Guanaratnam N, Cowen M: Correct and incorrect dosing of proton pump inhibitors and its impact on GERD symptoms. Gastroenterology 2003;124(suppl):A228.
147. Chey WD, Inadomi JM, Booher AM, Sharma VK, Fendrick AM, Howden CW: Primary-care physicians' perceptions and practices on the management of GERD: results of a national survey. Am J Gastroenterol 2005;100:1237-1242.
148. Anonymous: Omeprazole/antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05. Drugs R&D 2004;5:349-350.
149. Scarpignato C, Pelosini I, Molina E: Acid suppression in Barrett's esophagus: why and how? In Giuli R, Siewert JR, Couturier D, Scarpignato C (eds): Barrett's Esophagus. 250 Questions, 250 Answers. Paris, John Libbey Eurotext, 2003, vol 2, pp 437-455.
150. Lehmann F, Hildebrand P, Beglinger C: New molecular targets for treatment of peptic ulcer disease. Drugs 2003;63:1785-1797.
151. Flamel Technologies: Micropump® platform [http://www.flamel.com/ techAndProd/micropump.shtml]
152. AGI Therapeutics: Product AG-010 [http://www.agitherapeutics.com/agi010. html]
153. Freston JW, Kukulka MJ, Lloyd E, Lee C: A novel option in proton pump inhibitor dosing: lansoprazole orally disintegrating tablet dispersed in water and administered via nasogastric tube. Aliment Pharmacol Ther 2004;20:407-411.
154. Horn JR, Howden CW: Similarities and differences among delayed-release proton-pump inhibitor formulations. Aliment Pharmacol Ther 2005;22(suppl 3):20-24.
155. Maroni A, Zema L, Cerea M, Sangalli ME: Oral pulsatile drug delivery systems. Expert Opin Drug Deliv 2005;2:855-871.
156. Baldi F, Malfertheiner P: Lansoprazole fast disintegrating tablet: a new formulation for an established proton pump inhibitor. Digestion 2003;67:1-5.
157. Baldi F: Lansoprazole oro-dispersible tablet: pharmacokinetics and therapeutic use in acid-related disorders. Drugs 2005;65:1419-1426.
158. Freston JW, Chiu YL, Mulford DJ, Ballard ED: Comparative pharmacokinetics and safety of lansoprazole oral capsules and orally disintegrating tablets in healthy subjects. Aliment Pharmacol Ther 2003;17:361-367.
159. Baldi F, Ghersi S, Cavoli C, Torresan F: A comparison of the new lansoprazole orally disintegrating tablets with esomeprazole in patients with non-erosive reflux disease. Gastroenterology 2005; 128(suppl 2):A523-A524.
160. Santarus Inc. Corporate [http://www.santarus.com/corporate].
161. Hepburn B, Goldlust B: Comparative effects of an omeprazole antacid complex-immediate release and omeprazole delayed-release on omeprazole pharmacokinetics and gastric pH in healthy subjects. Gastroenterology 2003;124(suppl):A228.
162. Howden CW: Review article: immediate-release proton-pump inhibitor therapy - potential advantages. Aliment Pharmacol Ther 2005;22(suppl 3):25-30.
163. Tutuian R, Castell DO: Nocturnal acid breakthrough - approach to management. MedGenMed 2004;6:11 [http://www.medscape.com/viewarticle/490723].
164. Castell D, Bagin R, Goldlust B, Major J, Hepburn B: Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2005;21:1467-1474.
165. Castell D: Review of immediate-release omeprazole for the treatment of gastric acid-related disorders. Expert Opin Pharmacother 2005;6:2501-2510.
166. Stollman N, Metz DC: Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care 2005;20:35-45.
167. Metz DC: Preventing the gastrointestinal consequences of stress-related mucosal disease. Curr Med Res Opin 2005;21:11-18.
168. Conrad SA, Gabrielli A, Margolis B, Quartin A, Hata JS, Frank WO, Bagin RG, Rock JA, Hepburn B, Laine L: Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med 2005;33:760-765.
169. Zimbaro G, Ferraù O, Familiari L, Consolo F: Endogenous gastrin and insulin secretion in humans: effect of gastric lavage with sodium bicarbonate (in Italian). Boll Soc Ital Biol Sper 1973;49:896-901.
170. Feurle GE: The action of antacids on serum gastrin concentrations in man. Klin Wochenschr 1977;55:1039-1042.
171. Saito E, Matsuo Y: Inhibitory effect of leminoprazole on acid secretion in parietal cells isolated from guinea pig gastric mucosa. Jpn J Pharmacol 1995;68:19-23.
172. Takahashi S, Okabe S: The cytoprotective effect of leminoprazole on indomethacin-induced damage to rabbit gastric mucosal cells. J Pharmacol Exp Ther 1996;279:975-982.
173. Takahashi S, Okabe S: Mechanism by which orally administered leminoprazole stimulates mucus synthesis in rats. Pharmacology 1998;57:47-56.
174. Kwon D, Chae JB, Park CW, Kim YS, Lee SM, Kim EJ, Huh IH, Kim DY, Cho KD: Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo. Arzneimittelforschung 2001;51:204-213.
175. Kim EJ, Lee RK, Lee SM, Kim DY: General pharmacology of IY-81149, a new proton pump inhibitor. Arzneimittelforschung 2001;51:51-59.
176. Kil BJ, Kim IW, Shin CY, Jeong JH, Jun CH, Lee SM, Kim DY, Huh IH, Sohn UD: Comparison of IY-81149 with omeprazole in rat reflux oesophagitis. J Auton Pharmacol 2000;20:291-296.
177. Periclou AP, Goldwater R, Lee SM, Park DW, Kim DY, Cho KD, Boileau F,
178. Goldwater R, Lee SM, Chung GJ, Kim DY, Cho KD, Boileau F: A phase I, randomized, parallel placebo-controlled safety, tolerance and pharmacokinetic study of multiple doses of IY-8119 in fasting male volunteers. Clin Pharmacol Ther 1999;65:126(abstr PI-35).
179. +-ATPase inhibitor, on gastric acid secretion and gastroduodenal ulcers in rats. Methods Find Exp Clin Pharmacol 1999;21:115-122.
180. +-ATPase in vitro and in vivo. Biochem Pharmacol 2006;71:837-849.
181. +)-ATPase by proton pump inhibitors. J Am Chem Soc 2004;126:7800-7811.
182. Waldum HL, Lehy T, Brenna E, Sandvik AK, Petersen H, Sognen BS, Bonfils S, Lewin MJ: Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa. Scand J Gastroenterol 1991;26:23-35.
183. Kakinoki B, Ono C, Yamazaki N, Chikamatsu N, Wakatsuki D, Uchiyama K, Morinaka Y: General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl) methyl]sulfi-nyl]-1H- imidazo[4,5-b]pyridine. Methods Find Exp Clin Pharmacol 1999;21:179-187.
184. +-ATPase inhibitor, on gastric acid secretion in dogs. J Pharm Pharmacol 1999;51:457-464.
185. Negma-Lerads: Tenatoprazole (TU-199) Investigator's Brochure, Sept 2001.
186. Kim K, Johnson JA, Derendorf H: Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol 2004;44:1083-1095.
187. Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T: Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet 2005;20:153-167.
188. Domagala F, Ficheux H, Houin G, Barre J: Pharmacokinetics of tenatoprazole, a newly synthesized proton pump inhibitor, in healthy male Caucasian volunteers. Arzneimittelforschung 2006;56:33-39.
189. Galmiche JP, Bruley des Varannes S, Ducrotte P, Sacher-Huvelin S, Vavasseur F, Taccoen A, Fiorentini P, Homerin M: Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half-life: effects on intra-gastric pH and comparison with esomeprazole in healthy volunteers. Aliment Pharmacol Ther 2004;19:655-662.
190. Galmiche JP, Sacher-Huvelin S, Bruley des Varannes S, Vavasseur F, Taccoen A, Fiorentini P, Homerin M: A comparative study of the early effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric pH in healthy volunteers. Aliment Pharmacol Ther 2005;21:575-582.
191. Hunt RH, Armstrong D, James C, Chowdhury SK, Yuan Y, Fiorentini P, Taccoen A, Cohen P: Effect on intragastric pH of a PPI with a prolonged plasma half-life: comparison between tenatoprazole and esomeprazole on the duration of acid suppression in healthy male volunteers. Am J Gastroenterol 2005;100:1949-1956.
192. Lind T, Rydberg L, Kyleback A, Jonsson A, Andersson T, Hasselgren G, Holmberg J, Rohss K: Esomeprazole provides improved acid control vs. omeprazole in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000;14:861-867.
193. Bentley R: Role of sulfur chirality in the chemical processes of biology. Chem Soc Rev 2005;34:609-624.
194. Charbit S, Cohen A, Ficheux H, Homerin M, Schutze F, Taccoen A: Enantiomer (-) of tenatoprazole and the therapeutic use thereof. Patent No WO060891, 2004.
195. Miner PB Jr, Katz PO, Chen Y, Sostek M: Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study. Am J Gastroenterol 2003;98:2616-2620.
196. + limb of the pump cycle. J Biol Chem 1988;263:10705-10710.
197. Ene MD, Khan-Daneshmend T, Roberts CJ: A study of the inhibitory effects of SCH 28080 on gastric secretion in man. Br J Pharmacol 1982;76:389-391.
198. Beil W, Hackbarth I, Sewing KF: Mechanism of gastric antisecretory effect of SCH 28080. Br J Pharmacol 1986;88:19-23.
199. ClinicalTrials.gov. Ongoing trials with AZD 0865 [http://www. clinicaltrials.gov/ct/search;jsessionid=AAD3E3D625382610CF52EE75 696E5703?term=AZD0865&submit=Search]
200. Altana Group: Gastrointestinal projects [http://www.altana.com/root/ index.php?page_id=2025]
201. Park S, Ahn B, Lee B, Kang H, Song K: Pharmacokinetics of YH1885. Gut 2003;52:(suppl VI):A62.
202. +-ATPase selective, potassium competitive acid blocker. Gastroenterology 2004;126(suppl):A333.
203. Wurst W, Hartmann M: Current status of acid pump antagonists (reversible PPIs). Yale J Biol Med 1996;69:233-243.
204. Yu KS, Bae KS, Shon JH, Cho JY, Yi SY, Chung JY, Lim HS, Jang IJ, Shin SG, Song KS, Moon BS: Pharmacokinetic and pharmacodynamic evaluation of a novel proton pump inhibitor, YH1885, in healthy volunteers. J Clin Pharmacol 2004;44:73-82.
205. Nilsson C, Albrektson E, Rydholm H, Rohss K, Hassan-Alin M, Hasselgren G: Tolerability, pharmacokinetics and effects on gastric acid secretion after single oral doses of the potassium-competitive acid blocker AZD0865 in healthy male subjects. Gastroenterology 2005;128(suppl 2):A528.
206. Park S, Song K, Moon BS, Joo S, Choi M, Kim J, Choi K, Chung I, Sun H: The effect of 7 days of dosing with YH1885 on 24-hour intragastric acidity and plasma gastrin concentration in healthy male subjects. Gut 2002;51(suppl 3):A167.
207. Scarpignato C, Pelosini I: Antisecretory drugs for eradication of Helicobacter pylori: antibacterial activity and synergism with antimicrobial agents. Progr Basic Clin Pharmacol 1999;11:135-178.
208. Martinek J, Blum AL, Stolte M, Hartmann M, Verdu EF, Luhmann R, Dorta G, Wiesel P: Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Helicobacter pylori infection. Aliment Pharmacol Ther 1999;3:27-34.
209. Orexo AB: Product Portfolio [http://www.orexo.com/DynPage.aspx?id= 14994&mn1=1542&mn2=1619].
210. 2-receptor antagonist. Patent No W037256, 2004.
211. Patel SS, Wilde MI: Ebrotidine. Drugs 1996;51:974-980.
212. 2-receptors. Arzneimittelforschung 1997;47(suppl 4A):447-449.
213. Konturek PC, Brzozowski T, Konturek SI, Marquez M, Torres J, Ortiz JA: Studies on the cytoprotective and antisecretory activity of ebrotidine. A review. Arzneimittelforschung 1997;47(suppl 4A):578-589.
214. Slomiany BL, Piotrowski J, Slomiany A: Gastroprotective properties of ebrotidine. A review. Arzneimittelforschung 1997;47(suppl 4A):459-467.
215. Slomiany BL, Piotrowski J, Slomiany A: Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data. Arzneimittelforschung 1997;47(suppl 4A):475-482.
216. Matov V, Metchkov G, Krastev Z, Tchernev K, Mitova R, Marquez M, Torres J, Herrero E, Fillat O, Ortiz JA: Ebrotidine versus ranitidine in the treatment of acute duodenal ulcer. A multicentre, randomized, double-blind, controlled clinical trial. Arzneimittelforschung 1997;47(suppl 4A):555-559.
217. 2-receptor antagonist. J Hepatol 1999;31:641-646.
218. Pineda JA, Larrauri J, Macias J, Hernandez A, Guijarro J, Sayago M, Gavilan F, Aguilar J, Lissen E: Rapid progression to liver cirrhosis of toxic hepatitis due to ebrotidine. J Hepatol 1999;31:777-778.
219. Castillo JR, Torello J, Hernandez A: Liver injury caused by ebrotidine: a new example of the utility of the postmarketing surveillance. Eur J Clin Pharmacol 2000;56:187-189.
220. 2) receptor antagonist with gastroprotective activity. II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings. Chem Pharm Bull (Tokyo) 1998;46:616-622.
221. 2 receptor. Digestion 2001;64:155-160.
222. 2 receptor antagonist, in rats and dogs. Eur J Pharmacol 1993;235:245-253.
223. 2- receptor antagonist. Aliment Pharmacol Ther 2003;18:1149-1157.
224. 2 receptor antagonist, inhibits daytime acid secretion in both H. pylori infected and non infected human subjects. J Gastroenterol Hepatol 2002;17(suppl):A828.
225. 2-receptor antagonist, vs. lansoprazole in combination with amoxicillin and clarithromycin for eradication of Helicobacter pylori. Helicobacter 2003;8:111-119.
226. Inamori M, Togawa J, Iwasaki T, Ozawa Y, Kikuchi T, Muramatsu K, Chiguchi G, Matsumoto S, Kawamura H, Abe Y, Kirikoshi H, Kobayashi N, Shimamura T, Kubota K, Sakaguchi T, Saito S, Ueno N, Nakajima A: Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use? J Gastroenterol 2005;40:453-458.
227. Pantoflickova D, Dorta G, Ravic M, Jornod P, Blum AL: Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors. Aliment Pharmacol Ther 2003;17:1507-1514.
228. Haruki S, Matsumoto H, Kodama K, Takebe M, Takayanagi H, Cyong J: Pharmacokinetic studies of lafutidine (FRG-8813) in man (in Japanese). Jpn Pharmacol Ther 1995;23:179-189.
229. 2-receptor antagonists. Relationship between intrinsic potency and effective plasma concentrations. Clin Pharmacokinet 1991;20:218-236.
230. 2-receptor antagonists on human plasma levels of motilin, gastrin, secret in and somatostatin. Pharm Pharmacol Commun 1998;4:591-594.
231. Itoh H, Naito T, Takeyama M: Lafutidine changes levels of somatostatin, calcitonin gene-related peptide, and secretin in human plasma. Biol Pharm Bull 2002;25:379-382.
232. Taché Y, Raybould H, Wei JY: Central and peripheral actions of calcitonin gene-related peptide on gastric secretory and motor function. Adv Exp Med Biol 1991;298:183-198.
233. 2-receptor antagonist. Mucosal protection throughout gastrointestinal tract mediated by capsaicin-sensitive afferent neurons. Drug Des Rev 2004;1:133-144.
234. 2-receptor antagonist, on reflux esophagitis in rats through capsaicin-sensitive afferent neurons. J Pharmacol Sci 2003;93:55-61.
235. 2-receptor antagonist, against indomethacin-induced damage in rats - role of endogenous nitric oxide. Med Sci Monit 2001;7:869-877.
236. 2-receptor antagonist, on dextran sulfate sodium-induced colonie inflammation through capsaicin-sensitive afferent neurons in rats. Dig Dis Sci 2004;49:1696-1704.
237. Nozawa Y, Nishihara K, Akizawa Y, Orimoto N, Nakano M, Uji T, Ajioka H, Kanda A, Matsuura N, Kiniwa M: Lafutidine inhibits Helicobacter pylori-induced interleukin-8 production in human gastric epithelial cells. J Gastroenterol Hepatol 2004;19:506-511.
238. Pan C, Xu X, He H, Cai X, Zhang X: Separation and identification of cis and trans isomers of 2-butene-1,4-diol and lafutidine by HPLC and LC-MS. J Zhejiang Univ Sci B 2005;6:74-78.
239. Takeuchi K, Kato S: Prophylactic or treating agent for inflammatory enteropathy. Patent No JP 321366, 2003.
240. 2-receptor antagonist with mucosal protective properties. Dig Dis Sci 1991;36:1721-1728.
241. Dockray GJ: Gastrin. Best Pract Res Clin Endocrinol Metab 2004;18:555-568.
242. Bertaccini G: Peptides: gastrointestinal hormones. Gastrin; in Bertaccini G (ed): Gastrointestinal Motility: Mediators and Drugs. Berlin, Springer, 1982, vol 2, pp 11-40.
243. Koh TJ, Chen D: Gastrin as a growth factor in the gastrointestinal tract. Regul Pept 2000;93:37-44.
244. Rehfeld JF: Cholecystokinin. Best Pract Res Clin Endocrinol Metab 2004;18:569-586.
245. Wank SA: G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors: an exemplary family. Am J Physiol 1998;274:G607-G613.
246. Noble F, Wank SA, Crawley JN, Bradwejn J, Seroogy KB, Hamon M, Roques BP: International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors. Pharmacol Rev 1999;51:745-781.
247. Waldum HL, Kleveland PM, Sandvik AK, Brenna E, Syversen U, Bakke I, Tommeras K: The cellular localization of the cholecystokinin 2 (gastrin) receptor in the stomach. Pharmacol Toxicol 2002;91:359-362.
248. Zavros Y, Fleming WR, Hardy KJ, Shulkes A: Regulation of fundic and antral somatostatin secretion by CCK and gastrin. Am J Physiol 1998;274:G742-G750.
249. Kidd M, Modlin IM, Tang LH: Gastrin and the enterochromaffin-like cell: an acid update. Dig Surg 1998;15:209-217.
250. Reubi JC, Waser B, Horisberger U, Halter F, Soroka CJ, Kumar RR, Goldenring JR, Modlin IM: Identification of somatostatin and gastrin receptors on enterochromaffin-like cells from Mastomys gastric tumors. Endocrinology 1992;131:166-172.
251. Sandor A, Kidd M, Lawton GP, Miu K, Tang LH, Modlin IM: Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion. Gastroenterology 1996;110:1084-1092.
252. Scarpignato C: Cholecystokin antagonists and motilides. Pharmacology and potential in the treatment of gastroesophageal reflux disease and other digestive motor disorders. Front Gastrointest Res 1992;20:90-128.
253. 2 receptor antagonists: pharmacological tools to study the gastrin-ECL cell-parietal cell axis. Regul Pept 1999;80:1-12.
254. Herranz R: Cholecystokinin antagonists: pharmacological and therapeutic potential. Med Res Rev 2003;23:559-605.
255. Chambers MS, Fletcher SR: CCK-B antagonists in the control of anxiety and gastric acid secretion. Prog Med Chem 2000;37:45-81.
256. Weiss H: Proglumide after 10 years: a review of clinical results; in Weiss J, Miederer SE (eds): Proglumide and Other Gastrin Antagonists. Amsterdam, Elsevier, 1979, pp 113-131.
257. Hahne WF, Jensen RT, Lemp GF, Gardner JD: Proglumide and benzotript: members of a different class of cholecystokinin receptor antagonists. Proc Natl Acad Sci USA 1981;78:6304-6308.
258. Rovati LC: Pentanoic acid derivatives; in Adler G, Beglinger C (eds): Cholecystokinin Antagonists in Gastroenterology. Basic and Clinical Status. Berlin, Springer, 1991, pp 65-69.
259. 2 receptor antagonists. A review of pharmacological studies. I. Development of potential therapeutic tools for gastrin-related gastrointestinal diseases. Methods Find Exp Clin Pharmacol 1999;21:375-383.
260. Scarpignato C, Kisfalvi I, D'Amato M, Varga G: Effect of dexloxiglumide and spiroglumide, two new CCK-receptor antagonists, on gastric emptying and secretion in the rat: evaluation of their receptor selectivity in vivo. Aliment Pharmacol Ther 1996;10:411-419.
261. Revel L, Ferrari F, Makovec F, Rovati LC, Impicciatore M: Characterization of antigastrin activity in vivo of CR-2194, a new R-4-benzamido-5-oxo-pentanoic acid derivative. Eur J Pharmacol 1992;216:217-224.
262. Beltinger J, Hildebrand P, Drewe J, Christ A, Hlobil K, Ritz M, D'Amato M, Rovati L, Beglinger C: Effects of spiroglumide, a gastrin receptor antagonist, on acid secretion in humans. Eur J Clin Invest 1999;29:153-159.
263. Makovec F, Revel L, Letari O, Mennuni L, Impicciatore M: Characterization of antisecretory and antiulcer activity of CR-2945, a new potent and selective gastrin/CCK(B) receptor antagonist. Eur J Pharmacol 1999;369:81-90.
264. 2/gastrin receptor antagonist, inhibits gastrin stimulated gastric acid secretion in humans. Gut 2005;54(suppl VII):A36.
265. Dunlop J: CCK receptor antagonists. Gen Pharmacol 1998;31:519-524.
266. Lotti VJ, Chang RS: A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L365,260. Eur J Pharmacol 1989;162:273-280.
267. Pendley CE, Fitzpatrick LR, Ewing RW, Molino BF, Martin GE: The gastrin/cholecystokinin B receptor antagonist L-365,260 reduces basal acid secretion and prevents gastrointestinal damage induced by aspirin, ethanol and cysteamine in the rat. J Pharmacol Exp Ther 1993;265:1348-1354.
268. Nishida A, Yuki H, Tsutsumi R, Miyata K, Kamato T, Ito H, Yamano M, Honda K: L-365,260, a potent CCK-B/gastrin receptor antagonist, suppresses gastric acid secretion induced by histamine and bethanechol as well as pentagastrin in rats. Jpn J Pharmacol 1992;58:137-145.
269. Hirst BH, Elliott KJ, Ryder H, Szelke M: Inhibition of gastrin- and histamine-stimulated gastric acid secretion by gastrin and cholecystokinin antagonists in the rat. Aliment Pharmacol Ther 1991;5:31-39.
270. Varga G, Campbell DR, Bussjaeger LJ, Solomon TE: Role of gastrin and cholecystokinin receptors in regulation of peptone-stimulated gastric acid secretion in conscious rats. Eur J Pharmacol 1993;250:37-42.
271. Murphy MG, Sytnik B, Kovacs TO, Mertz H, Ewanik D, Shingo S, Lin JH, Gertz BJ, Walsh JH: The gastrin-receptor antagonist L-365,260 inhibits stimulated acid secretion in humans. Clin Pharmacol Ther 1993;54:533-539.
272. Grasing K, Freedholm D, Murphy MG, Swigar M, Russer T, Nosher J, Lin J, Frame V, Clarke L, Seibold JR: Selective blockade of cholecystokinin type B receptors with L-365,260 does not impair gallbladder contraction in normal humans. Am J Gastroenterol 1996;91:569-573.
273. Grasing K, Murphy MG, Lin J, Swigar M, Freedholm D, Clarke L, Zhang J, Wolkowitz OM, Weingartner H, Putnam K, Seibold JR: Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist. J Clin Pharmacol 1996;36:292-300.
274. Kramer MS, Cutler NR, Ballenger JC, Patterson WM, Mendels J, Chenault A, et al: A placebo-controlled trial of L-365,260, a CCK-B antagonist, in panic disorder. Biol Psychiatry 1995;37:462-466.
275. Bock MG, DiPardo RM, Mellin EC, Newton RC, Veber DF, Freedman SB, Smith AJ, Patel S, Kemp JA, Marshall GR, et al: Second-generation benzodiazepine CCK-B antagonists. Development of subnanomolar analogs with selectivity and water solubility. J Med Chem 1994;37:722-724.
276. Patel S, Chapman KL, Heald A, Smith AJ, Freedman SB: Measurement of central nervous system activity of systemically administered CCKB receptor antagonists by ex vivo binding. Eur J Pharmacol 1994;253:237-244.
277. Semple G, Ryder H, Rooker DP, Batt AR, Kendrick DA, Szelke M, Ohta M, Satoh M, Nishida A, Akuzawa S, Miyata K: (3R)-N-(1-(tert-butylcarbonylmethyl)-2, 3-dihydro-2-oxo-5-(2-pyridyl)-1H-1,4-benzodiazepin-3-yl)-N′-(3- (methylamino)phenyl)urea (YF476): a potent and orally active gastrin/CCK-B antagonist. J Med Chem 1997;40:331-341.
278. Takinami Y, Yuki H, Nishida A, Akuzawa S, Uchida A, Takemoto Y, Ohta M, Satoh M, Semple G, Miyata K: YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo. Aliment Pharmacol Ther 1997;11:113-120.
279. Takemoto Y, Yuki H, Nishida A, Ito H, Kobayashi-Uchida A, Takinami Y, Akuzawa S, Ohta M, Satoh M, Semple G, Miyata K: Effects of YF476, a potent and selective gastrin/cholecystokinin-B receptor antagonist, on gastric acid secretion in beagle dogs with gastric fistula. Arzneimittelforschung 1998;48:403-407.
280. Boyce M, Warrington S, Johnston A, Harris A: Effect on gastric pH of single doses of YF476, a new gastrin antagonist, compared with ranitidine and placebo. Br J Clin Pharmacol 2000;49:493P.
281. Boyce M, Warrington S, Johnston A, Harris A: Effect on gastric pH of repeated doses of YF476, a new gastrin antagonist, compared with omeprazole and placebo. Br J Clin Pharmacol 2000;50:383P-384P.
282. Boyce M, Warrington S, Lewis Y, Nentwich H, Harris A: Adaptation to the antisecretory effect of YF476, a new gastrin antagonist, in healthy men. Br J Clin Pharmacol 2001;53:437P.
283. 2) antagonist with excellent oral potency. Gastroenterology 2001;120(suppl 1):A311.
284. 2) receptor antagonist, on meal-induced acid secretion and experimental ulcer models in dogs and rats. Gastroenterology 2001;120(suppl 1):A331.
285. Schmassmann A, Reubi JC: Cholecystokinin-B/gastrin receptors enhance wound healing in the rat gastric mucosa. J Clin Invest 2000;106:1021-1029.
286. Jensen RT: Involvement of cholecystokinin/ gastrin-related peptides and their receptors in clinical gastrointestinal disorders. Pharmacol Toxicol 2002;91:333-350.
287. Aly A, Shulkes A, Baldwin GS: Gastrins, cholecystokinins and gastrointestinal cancer. Biochim Biophys Acta 2004;1704:1-10.
288. Waldum HL, Fossmark R, Bakke I, Martinsen TC, Qvigstad G: Hypergastrinemia in animals and man: causes and consequences. Scand J Gastroenterol 2004;39:505-509.
289. Waldum HL, Gustafsson B, Fossmark R, Qvigstad G: Antiulcer drugs and gastric cancer. Dig Dis Sci 2005;50(suppl 1):S39-S44.
290. Steel K: Gastrin and gastrin receptor ligands - a review of recent patent literature. IDrugs 2002;5:689-695.
291. Reubi JC, Schaer JC, Waser B: Cholecystokinin (CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res 1997;57:1377-1386.
292. Ferrand A, Wang TC: Gastrin and cancer: A review. Cancer Lett 2006 (in press).
293. Rengifo-Cam W, Singh P: Role of progastrins and gastrins and their receptors in GI and pancreatic cancers: targets for treatment. Curr Pharm Des 2004;10:2345-2358.
294. Anonymous: Gastrin 17 vaccine - Aphton: anti-gastrin 17 immunogen, G17DT. Biodrugs 2003;17:223-225.
295. Iwase K, Evers BM, Hellmich MR, Guo YS, Higashide S, Kim HJ, Townsend CM Jr: Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin. Gastroenterology 1997;113:782-790.
296. Brett BT, Smith SC, Bouvier CV, Michaeli D, Hochhauser D, Davidson BR, Kurzawinski TR, Watkinson AF, Van Someren N, Pounder RE, Caplin ME: Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer. J Clin Oncol 2002;20:4225-4231.
297. ClinicalTrials.gov. Ongoing Trials with G-17DT [http://www. clinicaltrials.gov/ct/search;jsessionid=65546F66B71B7A09A601C6258731D626?term= G-17DT]
298. Straathof JW, Lamers CB, Masclee AA: Effect of gastrin-17 on lower esophageal sphincter characteristics in man. Dig Dis Sci 1997;42:2547-2551.
299. Makishima R, Larkin D, Michaeli D, Gaginella T: Active immunization against gastrin17 with an N-terminal derived immunogen inhibits gastric and duodenal lesions in rats. Gastroenterology 1995;106:A824.
300. Justin T, Watson S, Michaeli D, Hardcastle J, Steele R: Gastric acid suppression using anti-gastrin 17 antibodies produced by a gastrin immunogen, Gastrimmune, in an in vivo pig model. Gastroenterology 1995;108:A125.
301. Smith AM, Morris T, Justin T, Michaeli D, Watson SA: Gastrimmune-induced antigastrin-17 antibodies inhibit acid secretion in a rat fistula model. Aliment Pharmacol Ther 2001;15:1981-1988.
302. Aphton Corp: Products [http://www.aphton.com/products.asp?aph=2]
303. Gevas P, Grimes S, Karr S, Michaelu D: Preparation of a medicament for the treatment of gastroesophageal reflux disease. EP1077716, 2001.
304. Modlin IM, Sachs G, Wright N, Kidd M: Edkins and a century of acid suppression. Digestion 2005;72:129-145.
305. 3 receptor drugs. Nat Rev Drug Discov 2005;4:107-120.
306. Degen LP, Peng F, Collet A, Rossi L, Ketterer S, Serrano Y, Larsen F, Beglinger C, Hildebrand P: Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit. Gastroenterology 2001;120:361-368.
307. Gibril F, Jensen RT: Zollinger-Ellison syndrome revisited: diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Curr Gastroenterol Rep 2004;6:454-463.
308. 2 receptor antagonist and proton pump inhibitor. Dig Dis Sci 1998;43:253-257.