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. 1989 Aug;30(8):1105–1109. doi: 10.1136/gut.30.8.1105

Frequent non-response to histamine H2-receptor antagonists in cirrhotics.

S Walker 1, D R Krishna 1, U Klotz 1, J C Bode 1
PMCID: PMC1434164  PMID: 2570008

Abstract

The effect of ranitidine 300 mg po given at 1800 h (famotidine 40 mg/cimetidine 800 mg) on the night time gastric pH was tested using longterm intragastric pH monitoring in 27 patients with and 32 patients without liver cirrhosis. A rise in the gastric pH above 4.0 for more than six hours between 1800 h and 0600 h was considered as sufficient effect (response) of the H2-receptor antagonists on gastric acidity. Among the patients with cirrhosis, there were significantly (p less than 0.005) more non-responders to ranitidine (16 of 27 patients) than in the control group (six of 32). When 13 of the 22 non-responders to ranitidine were subsequently treated with famotidine, only two showed a sufficient rise in their gastric pH. Of the 11 patients not responding to both H2-receptor antagonists, 10 were finally treated with cimetidine and eight did not respond. Plasma levels of all three drugs measured two and four hours after oral administration were not significantly different between cirrhotic and noncirrhotic patients as well as between responders and non-responders. In addition, in all patients plasma levels were far above the corresponding IC50 values. Therefore, differences in the absorption and plasma levels of these drugs cannot account for the frequent non-response in cirrhotics.

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Selected References

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  1. Albillos A., Abreu L., Alvarez-Mon M., Gea F., Gonzalo M. A., Rossi I., Garrido A., Barrios C., Escartín P. Study of the secretion of pepsinogen I in cirrhotic humans with and without portacaval shunt. Am J Gastroenterol. 1988 Jan;83(1):37–41. [PubMed] [Google Scholar]
  2. Arakawa T., Satoh H., Fukuda T., Nakamura H., Kobayashi K. Endogenous prostaglandin E2 in gastric mucosa of patients with alcoholic cirrhosis and portal hypertension. Gastroenterology. 1987 Jul;93(1):135–140. doi: 10.1016/0016-5085(87)90325-8. [DOI] [PubMed] [Google Scholar]
  3. Bauerfeind P., Cilluffo T., Emde C., Fimmel C., Kohler W., Gasser T., Blum A. L. Reduction of gastric acidity with ranitidine or famotidine: early evening dosage is more effective than late evening dosage. Digestion. 1987;37(4):217–222. doi: 10.1159/000199504. [DOI] [PubMed] [Google Scholar]
  4. Bauerfeind P., Cilluffo T., Fimmel C. J., Emde C., von Ritter C., Kohler W., Gugler R., Gasser T., Blum A. L. Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man? Gut. 1987 May;28(5):549–556. doi: 10.1136/gut.28.5.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Lazzari F., Mirakian R., Hammond L., Venturi C., Naccarato R., Bottazzo G. F. Gastric cell c-AMP stimulating autoantibodies in duodenal ulcer disease. Gut. 1988 Jan;29(1):94–100. doi: 10.1136/gut.29.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gladziwa U., Klotz U., Krishna D. R., Schmitt H., Glöckner W. M., Mann H. Pharmacokinetics and dynamics of famotidine in patients with renal failure. Br J Clin Pharmacol. 1988 Sep;26(3):315–321. doi: 10.1111/j.1365-2125.1988.tb05282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gledhill T., Buck M., Hunt R. H. Effect of no treatment, cimetidine 1 g/day, cimetidine 2 g/day and cimetidine combined with atropine on nocturnal gastric secretion in cimetidine non-responders. Gut. 1984 Nov;25(11):1211–1216. doi: 10.1136/gut.25.11.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gledhill T., Buck M., Paul A., Hunt R. H. Cimetidine or vagotomy? Comparison of the effects of proximal gastric vagotomy, cimetidine and placebo on nocturnal intragastric acidity and acid secretion in patients with cimetidine resistant duodenal ulcer. Br J Surg. 1983 Dec;70(12):704–706. doi: 10.1002/bjs.1800701203. [DOI] [PubMed] [Google Scholar]
  9. Gugler R., Rohner H. G., Somogyi A. A. Therapieversager unter Cimetidin beim Ulcus duodeni. Dtsch Med Wochenschr. 1982 Jul 9;107(27):1054–1057. doi: 10.1055/s-2008-1070073. [DOI] [PubMed] [Google Scholar]
  10. IRVINE W. T., DUTHIE H. L., RITCHIE H. D., WATON N. G. The liver's role in histamine absorption from the alimentary tract; its possible importance in cirrhosis. Lancet. 1959 May 23;1(7082):1064–1069. doi: 10.1016/s0140-6736(59)90650-6. [DOI] [PubMed] [Google Scholar]
  11. Jones D. B., Howden C. W., Burget D. W., Kerr G. D., Hunt R. H. Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs. Gut. 1987 Sep;28(9):1120–1127. doi: 10.1136/gut.28.9.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kirk A. P., Dooley J. S., Hunt R. H. Peptic ulceration in patients with chronic liver disease. Dig Dis Sci. 1980 Oct;25(10):756–760. doi: 10.1007/BF01345294. [DOI] [PubMed] [Google Scholar]
  13. Koop H., Klein M., Bauer A., Arnold R. Verminderte Säuresuppression unter Ranitidin bei schwerer Refluxösophagitis. Eine Pilotstudie. Z Gastroenterol. 1988 Jul;26(7):345–350. [PubMed] [Google Scholar]
  14. Morichau-Beauchant M., Houin G., Mavier P., Alexandre C., Dhumeaux D. Pharmacokinetics and bioavailability of ranitidine in normal subjects and cirrhotic patients. Dig Dis Sci. 1986 Feb;31(2):113–118. doi: 10.1007/BF01300694. [DOI] [PubMed] [Google Scholar]
  15. OSTROW J. D., TIMMERMAN R. J., GRAY S. J. Gastric secretion in human hepatic cirrhosis. Gastroenterology. 1960 Mar;38:303–313. [PubMed] [Google Scholar]
  16. Okolicsanyi L., Venuti M., Strazzabosco M., Orlando R., Nassuato G., Iemmolo R. M., Lirussi F., Muraca M., Pastorino A. M., Castelli G. Oral and intravenous pharmacokinetics of ranitidine in patients with liver cirrhosis. Int J Clin Pharmacol Ther Toxicol. 1984 Jun;22(6):329–332. [PubMed] [Google Scholar]
  17. Savarino V., Mela G. S., Scalabrini P., Di Timoteo E., Magnolia M. R., Celle G. Continuous 24-hour intragastric pH monitoring in the evaluation of the effect of a nightly dose of famotidine, ranitidine and placebo on gastric acidity of patients with duodenal ulcer. Digestion. 1987;37(2):103–109. doi: 10.1159/000199475. [DOI] [PubMed] [Google Scholar]
  18. Savarino V., Mela G. S., Scalabrini P., Magnolia M. R., Percario G., Di Timoteo E., Celle G. 24-H comparison between pH values of continuous intraluminal recording and simultaneous gastric aspiration. Scand J Gastroenterol. 1987 Mar;22(2):135–140. doi: 10.3109/00365528708991870. [DOI] [PubMed] [Google Scholar]
  19. Singer M. V., Leffmann C., Eysselein V. E., Calden H., Goebell H. Action of ethanol and some alcoholic beverages on gastric acid secretion and release of gastrin in humans. Gastroenterology. 1987 Dec;93(6):1247–1254. doi: 10.1016/0016-5085(87)90252-6. [DOI] [PubMed] [Google Scholar]
  20. Stopik D., Hampel K. E., Kleist D. v. Endogenes Plasma-Histamin und "hepatogenes" gastroduodenales Ulkus bei Leberzirrhose. Dtsch Med Wochenschr. 1977 Jun 24;102(25):932–933. doi: 10.1055/s-0028-1104991. [DOI] [PubMed] [Google Scholar]
  21. TABAQCHALI S., DAWSON A. M. PEPTIC ULCER AND GASTRIC SECRETION IN PATIENTS WITH LIVER DISEASE. Gut. 1964 Oct;5:417–421. doi: 10.1136/gut.5.5.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Young C. J., Daneshmend T. K., Roberts C. J. Effects of cirrhosis and ageing on the elimination and bioavailability of ranitidine. Gut. 1982 Oct;23(10):819–823. doi: 10.1136/gut.23.10.819. [DOI] [PMC free article] [PubMed] [Google Scholar]

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