Effect of repeated doses of netazepide, a gastrin receptor antagonist, omeprazole and placebo on 24h gastric acidity and gastrin in healthy subjects

British Journal of Clinical Pharmacology

Volumn 76, Issue 5, 2013, Pages 680-688

  Boyce, Malcolm ^a   Warrington, Steve ^a  

^a CENTRAL MIDDLESEX HOSPITAL   (United Kingdom)

Author keywords

Gastric pH; Gastrin receptor antagonist; Netazepide (YF476); Plasma gastrin

Indexed keywords

GASTRIN; NETAZEPIDE; OMEPRAZOLE; PLACEBO;

ABDOMINAL DISCOMFORT; ACHLORHYDRIA; ADULT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG TOLERANCE; DRUG WITHDRAWAL; FEMALE; GASTRIN BLOOD LEVEL; HUMAN; MALE; MORNING DOSAGE; NAUSEA; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REPEATED DRUG DOSE; SINGLE DRUG DOSE; STOMACH ACID SECRETION; STOMACH PH; TIME TO MAXIMUM PLASMA CONCENTRATION; TIME TO TREATMENT; TREATMENT WITHDRAWAL; UPREGULATION;

GASTRIC PH; GASTRIN RECEPTOR ANTAGONIST; NETAZEPIDE (YF476); PLASMA GASTRIN;

ADULT; BENZODIAZEPINONES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG TOLERANCE; FEMALE; GASTRIC ACIDITY DETERMINATION; GASTRINS; HUMANS; HYDROGEN-ION CONCENTRATION; MALE; OMEPRAZOLE; PHENYLUREA COMPOUNDS; PROTON PUMP INHIBITORS; RECEPTOR, CHOLECYSTOKININ B; TIME FACTORS; YOUNG ADULT;

EID: 84885044301     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12095     Document Type: Article

References (37)

1. Dockray G, Varro A, Dimaline R, Wang T. The gastrins: their production and biological activities. Ann Rev Physiol 2001; 63: 119-139.
2. Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology 2008; 134: 1842-1860.
3. Schmitz F, Göke M, Otte J, Schrader H, Reimann B, Kruse M, Siegel E, Peters J, Herzig K, Fölsch U, Schmidt W. Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa. Regul Pept 2001; 102: 101-110.
4. Chen D, Zhao C-M. Complexity of gastric acid secretion by targeted gene disruption in mice. Curr Pharm Des 2010; 16: 1235-1240.
5. Dimaline R, Varro A. Attack and defence in the gastric epithelium - a delicate balance. Exp Physiol 2007; 92: 591-601.
6. Almeida-Vega S, Catlow K, Dimaline R, Varro A. Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1. Am J Physiol 2009; 296: G414-G423.
7. Semple G, Ryder H, Rooker D, Batt A, Kendrick D, 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.
8. 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.
9. 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/CCK-B receptor antagonist, on gastric acid secretion in beagle dogs with gastric fistula. Arzneimittelforschung 1998; 48: 403-407.
10. Boyce M, David O, Darwin K, Mitchell T, Johnston A, Warrington S. Single oral doses of netazepide (YF476), a gastrin receptor antagonist, cause dose-dependent, sustained increases in 24-h gastric pH compared with placebo and ranitidine in healthy subjects. Aliment Pharmacol Ther 2012; 36: 181-189.
11. 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 [abstract]. Br J Clin Pharmacol 2000; 50: 383P-384.
12. Boyce M, Warrington S, Lewis Y, Nentwich H, Harris A. Adaptation to the antisecretory effect of YF476, a new gastrin antagonist, in healthy men [abstract]. Br J Clin Pharmacol 2002; 53: 437P.
13. Redrup M, Leaf F, Miyashita A, Watanabe T, Higuchi S, Chasseaud L, Cheng K. Validation of a liquid chromatographic-tandem mass spectrometric method for the measurement of (R)-1-[2, 3- dihydro-2-oxo-1-pivaloylmethyl-5-(2-pyridyl)-1H-1, 4-benzodiazepin-3-yl]-3-(3methylaminophenyl)urea (YF476) in human plasma. J Chromatogr 2002; 772: 317-325.
14. Takaishi S, Shibata W, Tomita H, Jin G, Yang X, Eriksen R, Dubeykovskaya Z, Asfaha S, Quante M, Betz K, Shulkes A, Wang T. In vivo analysis of mouse gastrin gene regulation in enhanced GFP-BAC transgenic mice. Am J Physiol Gastrointest Liver Physiol 2011; 300: G334-344.
15. 2-receptor antagonists. Dig Dis Sci 1999; 44: 1703-1709.
16. 2-blockade: placebo-controlled studies of 24-hour acidity and gastrin. Aliment Pharmacol Ther 1990; 4: (Suppl. 1): 47-63.
17. Qvigstad G, Arnestad JS, Brenna E, Waldum H. Treatment with proton pump inhibitors induces tolerance to histamine-2 receptor antagonists in Helicobacter pylori-negative patients. Scand J Gastroenterol 1998; 33: 1244-1248.
18. 2-receptor antagonist, SK&F 93479 trihydrochloride. Scand J Gastroenterol 1984; 101: (Suppl.): 103-108.
19. 2-antagonists SK&F 93479 and oxmetidine and omeprazole. Toxicol Pathol 1988; 16: 288-298.
20. Garner A, Fadlallah H, Parsons M. 1976 and all that! 20 years of antisecretory therapy. Gut 1996; 39: 784-786.
21. Ding X-Q, Lindström E, Håkanson R. Evaluation of three novel cholecystokinin-B/gastrin receptor antagonists: a study of their effects on rat stomach enterochromaffin-like cell activity. Pharmacol Toxicol 1997; 81: 232-237.
22. Chen D, Zhao C-M, Norlén P, Björkgvist M, Ding X, Kitano M, Håkanson R. Effect of CCK-2 receptor blockade on rat stomach ECL cells. Cell Tissue Res 2000; 299: 81-95.
23. Kitano M, Norlén P, Ding X-Q, Nakamura S, Håkanson R. Long-lasting CCK2 receptor blockade after a single subcutaneous injection of YF476 or YM022. Br J Pharmacol 2000; 130: 699-705.
24. Konagaya T, Bernsand M, Norlén P, Håkanson R. Mobilization of rat stomach ECL-cell histamine in response to short- or long-term treatment with omeprazole and/or YF 476 studied by gastric submucosal microdialysis in conscious rats. Br J Pharmacol 2001; 133: 37-42.
25. Björkqvist M, Dornonville de la Cour C, Zhao CM, Gagnemo-Persson R, Håkanson R, Norlén P. Role of gastrin in the development of gastric mucosa, ECL cells and A-like cells in newborn and young rats. Regul Pept 2002; 108: 73-82.
26. Martinsen T, Kawase S, Håkanson R, Torp S, Fossmark R, Qvigstad G, Sandvik A, Waldum H. Spontaneous ECL cell carcinomas in cotton rats: natural course and prevention by a gastrin receptor antagonist. Carcinogenesis 2003; 24: 1887-1896.
27. Takaishi S, Cui G, Frederick D, Carlson J, Houghton J, Varro A, Dockray G, Ge Z, Whary M, Rogers A, Fox J, Wang T. Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer. Gastroenterology 2005; 128: 1965-1983.
28. Cui G, Takaishi S, Ai W, Betz K, Florholmen J, Koh T, Houghton J, Pritchard D, Wang T. Gastrin-induced apoptosis contributes to carcinogenesis in the stomach. Lab Invest 2006; 86: 1037-1051.
29. Kidd M, Siddique Z, Drozdov I, Gustafsson B, Camp R, Black J, Boyce M, Modlin I. The CCK(2) receptor antagonist, YF476, inhibits Mastomys ECL-cell hyperplasia and gastric carcinoid tumor development. Regul Pept 2010; 162: 52-60.
30. Eissele R, Koop H, Bothe-Sandfort E, Arnold R. Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and somatostatin release in the rat stomach. Digestion 1992; 53: 179-188.
31. Nishida A, Kobayashi-Uchida A, Akuzawa S, Takinami Y, Shishido T, Kamato T, Ito H, Yamano M, Yuki H, Nagakura Y, Honda K, Miyata K. Gastrin receptor antagonist YM022 prevents hypersecretion after long term acid suppression. Am J Physiol 1995; 269: G699-G705.
32. Korman M, Hansky J, Scott P. Serum gastrin in duodenal ulcer. iii. Influence of vagotomy and pylorectomy. Gut 1972; 13: 39-42.
33. Hollinshead J, Debas H, Yamada T, Elashoff J, Osadchey B, Walsh J. Hypergastrinaemia develops within 24 hours of truncal vagotomy in dogs. Gastroenterology 1985; 88: 35-40.
34. Burkitt M, Pritchard D. Pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther 2006; 24: 1305-1320.
35. Boyce M, Warrington S, Black J. Netazepide, a gastrin receptor antagonist, causes dose-dependent, persistent inhibition of the responses to pentagastrin in healthy subjects. Br J Clin Pharmacol. in press.
36. van Herwaarden M, Samson M, Smout A. 24-h recording of intragastric pH: technical aspects and clinical relevance. Scand J Gastroenterol 1999; 230: 9-16.
37. Johnston D, Wormsley K. Problems with the interpretation of pH measurements. Clin Investig 1993; 72: 12-17.