Skip to main content
NCBI home page
Gut logoLink to Gut
. 1994 Jun;35(6):750–754. doi: 10.1136/gut.35.6.750

Maintenance of intragastric pH > 4 with famotidine in duodenal ulcer patients: factors influencing drug requirements.

J C Delchier 1, F Roudot-Thoraval 1, L Stanescu 1, M C Deharvengt 1, L Elouaer Blanc 1
PMCID: PMC1374871  PMID: 8020798

Abstract

The gastrojet, a closed loop pH feedback infusion pump capable of maintaining intragastric pH at a target value by infusing H2 blockers at variable rates, was used to assess factors influencing the quantity of famotidine required to maintain intragastric pH above 4 for 24 hours in 34 fed patients with duodenal ulcers. The following factors were considered: sex, age, duration of the disease, previous bleeding, previous poor response to H2 blockers (ulcer unhealed at six weeks, or recurrence within three months during maintenance treatment), activity of the ulcer disease, smoking habits, cirrhosis. The patients had taken no antisecretory drugs for the 15 days before the study. Two standardised meals were given during the study period (from 1000 to 1000). Fifty ml of famotidine (4 mg/ml) was loaded into infusion bags and the pump was programmed to deliver the drug intravenously at 11 rates varying from 0 to 40 microliters/min. The target pH was 4. Mean famotidine use was 111 mg (range 33 to 200), the 23 hour median pH was 5.3, and the mean time during which pH was above 4 was 75.4%. There was a negative correlation (p < 0.001) between famotidine delivery and the inhibition of gastric acidity. Statistical analysis showed that only cirrhosis significantly influenced drug delivery, median pH, and the time during which pH was above 4. Mean drug delivery in the cirrhotic and non-cirrhotic patients was 135 v 97 mg (p < 0.04), 23 hour median pH was 4.7 v 5.6 (p < 0.01), and the mean time at pH > 4 was 65.9 v 81.6% (p < 0.01). There were large interindividual variations in famotidine requirements, but not only cirrhosis was predictive of dose requirement. These results suggest that the appropriate amount of famotidine to treat duodenal ulcer in cirrhotic patients is probably higher than the usually recommended dose.

Full text

PDF
750

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. 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]
  3. Bernardi M., Trevisani F., De Palma R., Ligabue A., Capani F., Baraldini M., Gasbarrini G. Chronobiological evaluation of sympathoadrenergic function in cirrhosis. Relationship with arterial pressure and heart rate. Gastroenterology. 1987 Dec;93(6):1178–1186. doi: 10.1016/0016-5085(87)90242-3. [DOI] [PubMed] [Google Scholar]
  4. Boyd E. J., Wilson J. A., Wormsley K. G. Smoking impairs therapeutic gastric inhibition. Lancet. 1983 Jan 15;1(8316):95–97. doi: 10.1016/s0140-6736(83)91742-7. [DOI] [PubMed] [Google Scholar]
  5. Burget D. W., Chiverton S. G., Hunt R. H. 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 Aug;99(2):345–351. doi: 10.1016/0016-5085(90)91015-x. [DOI] [PubMed] [Google Scholar]
  6. Cargill J. M., Saunders J. H., Peden N., Wormsley K. G. Very long-term treatment of peptic ulcer with cimetidine. Lancet. 1978 Nov 25;2(8100):1113–1115. doi: 10.1016/s0140-6736(78)92273-0. [DOI] [PubMed] [Google Scholar]
  7. Collen M. J., Stanczak V. J., Ciarleglio C. A. Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication). Dig Dis Sci. 1989 Feb;34(2):233–237. doi: 10.1007/BF01536057. [DOI] [PubMed] [Google Scholar]
  8. Corazziari E., Bontempo I., Anzini F., Torsoli A. Motor activity of the distal oesophagus and gastrooesophageal reflux. Gut. 1984 Jan;25(1):7–13. doi: 10.1136/gut.25.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Di Mario F., Gottardello L., Germanà B., Dotto P., Grassi S. A., Vianello F., Battaglia G., Leandro G., Burra P., Salvagnini M. Peptic ulcer in cirrhotic patients: a short- and long-term study with antisecretory drugs. Ital J Gastroenterol. 1992 Mar-Apr;24(3):122–125. [PubMed] [Google Scholar]
  10. Galmiche J. P., Tranvouez J. L., Denis P., N'Djitoyap C., Guillard J. F., Lehur P. A., Colin R. L'enregistrement nocturne du pH gastrique permet-il de prévoir la réponse thérapeutique des ulcères duodénaux sévères traités par la ranitidine? Gastroenterol Clin Biol. 1985 Aug-Sep;9(8-9):583–589. [PubMed] [Google Scholar]
  11. Gaur S. K., Vij J. C., Sarin S. K., Anand B. S. Gastric secretion in cirrhosis and non-cirrhotic portal fibrosis. Digestion. 1988;39(3):151–155. doi: 10.1159/000199619. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Hannan A., Chesner I., Merki H. S., Mann S., Walt R. P. Use of automatic computerised pump to maintain constant intragastric pH. Gut. 1990 Nov;31(11):1246–1249. doi: 10.1136/gut.31.11.1246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Korman M. G., Hansky J., Eaves E. R., Schmidt G. T. Influence of cigarette smoking on healing and relapse in duodenal ulcer disease. Gastroenterology. 1983 Oct;85(4):871–874. [PubMed] [Google Scholar]
  16. Merki H. S., Fimmel C. J., Walt R. P., Harre K., Röhmel J., Witzel L. Pattern of 24 hour intragastric acidity in active duodenal ulcer disease and in healthy controls. Gut. 1988 Nov;29(11):1583–1587. doi: 10.1136/gut.29.11.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Merki H. S., Halter F., Wilder-Smith C., Allemann P., Witzel L., Kempf M., Roehmel J., Walt R. P. Effect of food on H2-receptor blockade in normal subjects and duodenal ulcer patients. Gut. 1990 Feb;31(2):148–150. doi: 10.1136/gut.31.2.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Merki H. S., Wilder-Smith C. H., Walt R. P., Halter F. The cephalic and gastric phases of gastric secretion during H2-antagonist treatment. Gastroenterology. 1991 Sep;101(3):599–606. doi: 10.1016/0016-5085(91)90515-m. [DOI] [PubMed] [Google Scholar]
  19. Merki H. S., Witzel L., Kaufman D., Kempf M., Neumann J., Röhmel J., Walt R. P. Continuous intravenous infusions of famotidine maintain high intragastric pH in duodenal ulcer. Gut. 1988 Apr;29(4):453–457. doi: 10.1136/gut.29.4.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morgan M. Y., Stambuk D. Famotidine pharmacokinetics following oral and intravenous administration in patients with liver disease: results of a preliminary study. Postgrad Med J. 1986;62 (Suppl 2):29–37. [PubMed] [Google Scholar]
  21. 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]
  22. Sacchetti C., Capello M., Rebecchi P., Roncucci L., Zanghieri G., Tripodi A., Ponz de Leon M. Frequency of upper gastrointestinal lesions in patients with liver cirrhosis. Dig Dis Sci. 1988 Oct;33(10):1218–1222. doi: 10.1007/BF01536669. [DOI] [PubMed] [Google Scholar]
  23. Sonnenberg A., Müller-Lissner S. A., Vogel E., Schmid P., Gonvers J. J., Peter P., Strohmeyer G., Blum A. L. Predictors of duodenal ulcer healing and relapse. Gastroenterology. 1981 Dec;81(6):1061–1067. [PubMed] [Google Scholar]
  24. Sontag S., Graham D. Y., Belsito A., Weiss J., Farley A., Grunt R., Cohen N., Kinnear D., Davis W., Archambault A. Cimetidine, cigarette smoking, and recurrence of duodenal ulcer. N Engl J Med. 1984 Sep 13;311(11):689–693. doi: 10.1056/NEJM198409133111101. [DOI] [PubMed] [Google Scholar]
  25. Trevisani F., Bernardi M., De Palma R., Pancione L., Capani F., Baraldini M., Ligabue A., Gasbarrini G. Circadian variation in renal sodium and potassium handling in cirrhosis. The role of aldosterone, cortisol, sympathoadrenergic tone, and intratubular factors. Gastroenterology. 1989 Apr;96(4):1187–1198. doi: 10.1016/0016-5085(89)91640-5. [DOI] [PubMed] [Google Scholar]
  26. Wagner S., Gladziwa U., Gebel M., Schüler A., Freise J., Schmidt F. W. Circadian pattern of intragastric acidity in duodenal ulcer patients: a study of variations in relation to ulcer activity. Gut. 1991 Oct;32(10):1104–1109. doi: 10.1136/gut.32.10.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Walker S., Krishna D. R., Klotz U., Bode J. C. Frequent non-response to histamine H2-receptor antagonists in cirrhotics. Gut. 1989 Aug;30(8):1105–1109. doi: 10.1136/gut.30.8.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weiler H., Weiler C., Gerok W. Gastric mucosal prostaglandin E2 levels in cirrhosis and portal hypertension. J Hepatol. 1990 Jul;11(1):58–64. doi: 10.1016/0168-8278(90)90272-s. [DOI] [PubMed] [Google Scholar]
  29. 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]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES