Gastric acid inhibitory profile of ebrotidine, a novel H2-receptor antagonist in humans

• Autorzy: Maczka M , Kwiecien N. , Obtulowicz W. , Konturek S.J. , Kaminski K. , Oleksy J. , Gabryelewicz A. , Torres J.
• Języki publikacji: EN

Abstrakty

EN

This study was designed to assess the gastric secretory effects of ebrotidine, a novel H₂ receptor antagonist, in humans. Three groups (A, В and C) of male subjects with normal gastric mucosa were used. Group A (6 subjects) was used to determine the dose-dependency of gastric inhibitory effect of ebrotidine on basal and pentagastrin- induced maximal acid output. Group В (8 subjects) was employed to examine the duration of the inhibitory effect of ebrotidine on basal and pentagastrin-induced acid secretion. In group C (6 subjects), the 24 h pH-metry was assessed using intraluminal pH-electrode placed in the gastric corpus and connected to a portable recording unit. Single oral dose of ebrotidine (200, 400 or 800 mg) caused a dose- dependent reduction in basal and pentagastrin-induced acid secretion that at a dose of 800 mg amounted to about 89% and 93%, respectively. This inhibition was still observed after 6h and averaged 72% and 50%, respectively. After 12 and 24 h upon the drug intake, both basal and pentagastrin-induced acid secretion returned to the control values. Single oral dose of ebrotidine (800 mg) caused a significant reduction in circadian acidity and resulted in a marked and significant reduction of intragastric acidity for about 6 h upon the administration. This inhibition was accompanied by a transient increase in basal and postprandial gastrin levels. We conclude that ebrotidine is highly effective inhibitor of basal, pentagastrin-induced and circadian gastric acid secretion in humans.

Słowa kluczowe

EN

histamine; man; ebrotidine; gastric acid; stomach; gastrin

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 1992
• Tom: 43
• Numer: 2
• Opis fizyczny: p.139-148,fig.

Twórcy

autor

Maczka M

• University Medical School, 31-531 Krakow, Grzegorzecka 16, Poland

autor

Kwiecien N.

autor

Obtulowicz W.

autor

Konturek S.J.

autor

Kaminski K.

autor

Oleksy J.

autor

Gabryelewicz A.

autor

Torres J.

Bibliografia

• 1. Anglada A, Marguez M, Sacristan A, Oritz JA. Inhibitors of gastric acid secretion: N-sulphonyl formamidines in a series of new histamine H₂-receptor antagonists. Eur J Med Chem 1988; 3: 97-100.
• 2. Konturek SJ, Brzozowski T, Drozdowicz D, Majka J. Ebrotidine, a novel H₂-receptor antagonist with local gastroprotective activity. Eur J Gastroenterol Hepat 1991; 3: 941-947.
• 3. Savarino V, Mela GS, Scalabrini P et al. Continuous 24 hour intragastric pH monitoring: focus on reproducibility in duodenal ulcer patients. Gastroenterol Clin Biol 1986; 10: 826-830.
• 4. Savarino V. Continuous intragastric pH monitoring a real progress in the assessment antisecretory drugs. Ital J Gastroenterol 1990; 22: Suppl 2: 20-23.
• 5. Konturek SJ, Kwiecień N, Obtułowicz W et al. Cephalic phase of gastric secretion in healthy subjects and duodenal ulcer patients: role of vagal innervation. Gut 1979; 20: 875-881.
• 6. Konturek SJ, Mączka J, Kamiński K, Sito E, Oleksy J. Gastroprotective and antisecretory activities of ebrotidine. Scand J Gastroenterol 1992 (in press).
• 7. Graham DY. The relationship between nonsteroidal antiinflammatory drugs and peptic ulcer disease. Gastroenterology Clinics NA. 1990; 19: 171-182.
• 8. Thompson ABR. Acid secretion and acid suppression in pathogenesis and healing of peptic ulcer disease. Hepato-Gastroenterology 1990; 37: (Suppl 1): 18-28.
• 9. Freston JW. Overview of medical therapy of peptic ulcer disease. Gastroenterology Clinics N. A. 1990; 19: 121-140.
• 10. Feldman M, Richardson CT. Total 24-hour gastric acid secretion in patients with duodenal ulcer: Comparison with normal subjects and effects of cimetidine and parietal cell vagotomy. Gastroenterology 1986; 90: 540-544.
• 11. Blair AJ, Feldman M, Barnett C. Detailed comparison of basal and food-stimulated gastric acid secretion rates and serum gastrin concentrations in duodenal ulcer patients and normal subjects. J Clin Invest 1987; 79: 582-587.
• 12. Gledhill T, Howard OM, Buck M. Single nocturnal doses of an H₂-receptor antagonist for the treatment of duodenal ulcer. Gut 1983; 24: 904-908.
• 13. Jones B, Howden CW, Burget DW, Kerr GH, Hunt RH. Acid suppression in duodenal ulcer. A meta-analysis to define optimal dosing with antisecretory drugs. Gut 1987; 28: 1120-1127.
• 14. Konturek SJ, Obtułowicz W, Kwiecień N, Sito, Oleksy J, Miszczuk-Jamska B. Effect of ranitidine, a new H₂ -antagonist, on gastric and pancreatic secretion in duodenal ulcer patients. Dig Dis Sci 1980; 25: 737-743.
• 15. Merki HS, Witzel L, Walt RP et al. Day to day variations of 24-hour intragastric acidity. Gastroenterology 1988; 94: 887-891.
• 16. Etienne A, Fimmel CJ, Bron BA, Loizeau E, Blum A. Evaluation of pirenzepine on gastric acidity in healthy volunteers using ambulatory pH-monitoring. Gut 1985; 26: 241-245.
• 17. Merki HS, Witzel L, Harre K, Scheurle E, Neuman J, Rohmel J. Single oral dose tratment with H-receptor antagonists. Is the bedtime administration too late? Gut 1987; 28: 451-454.
• 18. Merki HS, Bender W, Labs R. Safety and efficacy of roxatidine acetate. Evidence from pharmacodynamic and clinical trials. J Clin Gastroenterol 1988; 11: (Supp 1): S20-23.
• 19. Moore JG, Haiberg F. Circadian rhythm of gastric acid secretion in men with active duodenal ulcer. Dig Dis Sci 1986; 31: 1185-1191.
• 20. Savarino V. 24-hour of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry. Dig Dis Sci 1988; 33: 1077-1080.