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Drugs

, Volume 24, Issue 4, pp 267–303 | Cite as

Ranitidine: A Review of its Pharmacology and Therapeutic Use in Peptic Ulcer Disease and Other Allied Diseases

  • R. N. Brogden
  • A. A. Carmine
  • R. C. Heel
  • T. M. Speight
  • G. S. Avery
Drug Evaluations

Summary

Synopsis

Ranitidine 1 is a new histamine H2-receptor antagonist which, unlike cimetidine, does not contain an imidazole group. On a weight basis, ranitidine is 4 to 10 times more potent than cimetidine in inhibiting stimulated gastric acid secretion in humans.

Therapeutic trials comparing ranitidine and cimetidine have demonstrated that ranitidine 150mg twice daily is an effective alternative to cimetidine 1000mg daily in 4 divided doses in increasing the rate of healing of duodenal and gastric ulcers over a period of 4 to 6 weeks. Ranitidine, given as a single 150mg dose at night, decreases the incidence of ulcer recurrence. Preliminary studies in the Zollinger-Ellison syndrome and in patients intolerant of, or unresponsive to cimetidine, indicate that ranitidine controls the gastric hyperacidity and heals most ulcers, including those which failed to respond to months of treatment with cimetidine 1 to 1.6g daily.

Ranitidine, unlike cimetidine, has no antiandrogenic effects and does not alter hepatic metabolism of drugs.

Ranitidine is well tolerated. Preliminary reports of the resolution of cimetidine-induced adverse effects following substitution of ranitidine, suggest that ranitidine may be of value in patients intolerant of cimetidine. However, wider clinical experience with ranitidine is needed to determine the clinical relevance of these reports.

Pharmacodynamic Studies

Studies in animals have shown ranitidine to be a competitive inhibitor of histamine at histamine H2-receptor sites. In vitro and in vivo it is more active than cimetidine on a molar basis. In humans, ranitidine inhibits basal gastric acid secretion and that stimulated by pentagastrin, histamine and normal meals, being about 4 to 10 times more active than cimetidine in healthy subjects and in patients with duodenal ulcer. Single oral doses of ranitidine 50, 100, 150 and 200mg reduced pentagastrin-stimulated mean acid output by 42, 75, 85 and 95% respectively in healthy subjects. After a single 150mg oral dose of ranitidine, basal gastric acid secretion was inhibited by 70% and 38%, at 5 and 10 hours. In patients with duodenal ulcer, oral ranitidine 150mg twice daily produced a 70% reduction in 24-hour intragastric acidity. Nocturnal acid output decreased by 90%.

Under conditions similar to those in clinical practice, 24-hour acidity was decreased by 69% and 71% with ranitidine 300mg and 400mg daily, respectively. Cimetidine 1000mg daily reduced 24-hour gastric acidity by 48%.

In healthy subjects and duodenal ulcer patients, ranitidine administration did not significantly alter serum gastrin, pancreatic or mucus secretion. Pepsin output is decreased.

Serum prolactin secretion is not usually increased by either acute or repeated administration of usual therapeutic doses of ranitidine but concentrations are elevated after intravenous injection of a 300mg dose. Unlike cimetidine, ranitidine does not have antiandrogen effects in animals or humans, and studies to date suggest that ranitidine does not affect hepatic metabolism of drugs.

Pharmacokinetics

After oral administration, peak plasma concentrations are achieved within 1 to 2 hours and are not influenced by food. After a 150mg oral dose, mean peak plasma concentrations are about 400 ng/ml. Reported bioavailability after single doses has varied between about 40 and 88% but has most often been around 50%. Bioavailability and hepatic clearance values suggest significant ‘first-pass’ metabolism after oral administration. The apparent volume of distribution is 1.2 to 1.8 L/kg. In healthy subjects the cerebrospinal fluid concentration of ranitidine is one-twentieth to one-thirtieth of that in plasma sampled at the same time. Ranitidine is 15% protein bound. The majority of an oral or intravenous dose of ranitidine that is excreted in the urine is in the form of unchanged drug. Hepatic clearance is about 30% of total body clearance after intravenous injection and up to 73% after oral administration. After repeated oral doses the elimination half-life of ranitidine is 2.25 hours. Recent studies of the relationship between plasma concentration and inhibition of acid secretion indicate that a ranitidine concentration of around 160 ng/ml is required for 50% inhibition of pentagastrin-stimulated secretion over a 2-hour period.

Therapeutic Trials

In open trials, placebo-controlled trials and comparative trials with cimetidine, the rate of healing of duodenal ulcers after 4 weeks’ treatment has ranged between 60 and 100%. Ranitidine 150mg twice daily, the dose administered in most studies, has been demonstrated to be more effective than placebo and usually not significantly different from cimetidine 1000mg daily in 4 divided doses. In placebo-controlled studies the rate of ulcer healing with placebo has ranged from 27 to 46%. As has been found with other treatments effective in accelerating the healing of peptic ulcer, pain generally decreased as healing progressed, but there was no good correlation between the presence or absence of symptoms and endoscopic ulcer healing.

Comparisons with cimetidine have usually been single blind, with the endoscopist being unaware of the individual patient’s treatment. No significant difference between ranitidine 300mg daily and cimetidine 1000mg daily was found in all except one large multicentre study. This study found ranitidine to be the more effective drug in accelerating the healing of duodenal ulcer after 4 weeks’ treatment, although the healing rates were not greatly different (74 and 68%). Other studies have reported a healing rate at 4 weeks, of 63 to 77% in patients treated with ranitidine 300mg daily and of 60 to 84% in patients receiving 1000mg daily of cimetidine. After 8 weeks of treatment, healing rates have ranged from 85 to 92% with ranitidine and from 88 to 95% with cimetidine.

Ranitidine 300mg daily has been used successfully in the treatment of peptic ulceration which had persisted despite treatment with cimetidine 1 to 1.6g daily for 2 to 36 months.

Placebo-controlled studies have demonstrated the efficacy of ranitidine 150mg twice daily in increasing the rate of healing of gastric ulcers. The healing rate with ranitidine has ranged from 59 to 76% after 3 or 4 weeks’ treatment, whilst with placebo, the healing rate was 23 to 44%. Comparisons with cimetidine have found no significant differences between ranitidine and cimetidine with respect to healing rates or tolerability.

Recently conducted placebo-controlled trials and comparisons with cimetidine, indicate that ranitidine 150mg as a single dose at night decreases the rate of duodenal ulcer recurrence. After 12 months of maintenance treatment with either ranitidine 150mg or cimetidine 400mg, the rate of ulcer recurrence was 25% with ranitidine and 24% with cimetidine.

Studies in patients with reflux oesophagitis, which was confirmed by endoscopy and biopsy, have consistently shown ranitidine 150mg twice daily to be superior to placebo in improving the endoscopic appearance of oesophagitis.

Preliminary studies in the Zollinger-Ellison syndrome in patients intolerant of cimetidine, have shown ranitidine at doses of up to 900mg daily, to control symptoms over prolonged periods and to heal the ulcers, without causing troublesome side effects.

Initial studies of ranitidine in the treatment and prevention of acute upper gastrointestinal bleeding in acutely ill patients, have been too small to permit any clear conclusions regarding the possible beneficial effects of the drug, although results from some studies have been encouraging in patients with duodenal ulcer.

Side Effects

In short term controlled and open studies in the treatment of peptic ulceration, and in patients treated for longer periods, ranitidine 100 to 150mg twice daily has been well tolerated with side effects such as skin rash, headache and dizziness having been reported in a total of 3% of patients. In individual case reports, ranitidine has been substituted for cimetidine in patients intolerant of this drug, without causing a recurrence of gynaecomastia and sexual impotence.

Dosage

The usual oral adult dose of ranitidine is 150mg twice daily in the treatment of duodenal or benign gastric ulcer. Treatment should be continued until the ulcer has healed, or if endoscopic reassessment is not possible, for 4 to 8 weeks. In limited experience in treatment of the Zollinger-Ellison syndrome, the dosage of ranitidine has been 600 to 900mg daily in divided doses. Ranitidine 150mg at night is used as maintenance treatment to prevent ulcer recurrence.

Dosage should be decreased in patients with impaired renal function.

Keywords

Cimetidine Duodenal Ulcer Ranitidine Gastric Ulcer Gastric Acid Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Andrews, A.D.; Brock-Utne, J.G. and Downing, J.W.: Protection against pulmonary acid aspiration with ranitidine. Anaesthesia 37: 22 (1982).PubMedGoogle Scholar
  2. Ashton, M.G.; Holdsworth, C.D.; Ryan, F.P. and Moore, M.: Healing of gastric ulcers after one, two and three months of ranitidine. British Medical Journal 284: 467 (1982).PubMedGoogle Scholar
  3. Avella, J.; Binder, H.J.; Madsen, J.E. and Askenase, P.W.: Effect of histamine H2-receptor antagonist on delayed hypersensitivity. Lancet 1: 624–626 (1978).PubMedGoogle Scholar
  4. Barbier, P.; Dumont, A. and Adler, M.: Evaluation on etude ouverte de la ranitidine dans la therapeutique de 40 ulcerations gastro-duodenales. Acta Gastro-Enterologica Belgica 42: 268 (1979).PubMedGoogle Scholar
  5. Barr, G.D.; Gellatly, R.; Paris, C. and Piper, D.W.: Comparison of ranitidine and cimetidine in duodenal ulcer. Abstract. Gastroenterology 80(5, part 20): 1104 (1981).Google Scholar
  6. Barr, G.D.; Paris, C.H.; Middleton, W.R.J. and Piper, D.W.: Comparison of ranitidine with cimetidine in duodenal ulcer healing; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 146–151 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  7. Barr, G.D. and Piper, D.W.: Possible ranitidine hepatitis. Medical Journal of Australia 2: 421 (1981).PubMedGoogle Scholar
  8. Bateson, M.C.; Browning, M.C.K. and Maconnachie, A.: Galactorrhoea with cimetidine. Lancet 2: 247 (1977).PubMedGoogle Scholar
  9. Belgian Peptic Ulcer Study Group: An interim report on a single-blind comparative study of ranitidine and cimetidine in patients with gastric ulcer; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.204–211 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  10. Berstad, A.: Overview of ranitidine in reflux oesophagitis: its effect on symptoms, endoscopic appearance and histology; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.295–302 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  11. Berstad, A.; Kett, K.; Aadland, E.; Carlsen, E.; Frislid, K.; Saxhaug, K. and Kruse-Jensen, A.: Treatment of duodenal ulcer with ranitidine, a new histamine H2-receptor antagonist. Scandinavian Journal of Gastroenterology 15: 637 (1980).PubMedGoogle Scholar
  12. Berstad, A.; Rydning, A.; Kolstad, B. and Frislid, K.: Reduction of postprandial gastric acidity and pepsin concentration by ranitidine and antacids in healthy volunteers. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 67 (1981).Google Scholar
  13. Bertaccini, G.; Molina, E.; Bobblio, P. and Foggi, E.: Ranitidine increases lower oesophageal sphincter pressure in man. Italian Journal of Gastroenterology 13: 147 (1981).Google Scholar
  14. Bianchi Porro, G.; Grossi, E.; Petrillo, M. and Sangaletti, O.: Basal acid output response to ranitidine in duodenal ulcer patients. Italian Journal of Gastroenterology 12: 150 (1980).Google Scholar
  15. Bodemar, G.; Norlander, B. and Wolan, A.: Pharmacokinetics of cimetidine after single doses and during treatment. Clinical Pharmacokinetics 6: 306 (1981).PubMedGoogle Scholar
  16. Bogues, K.; Dixon, G.T.; Fowler, P.; Jenner, W.N.; Maconochie, J.G.; Martin, L.E. and Willoughby, B.A.: Pharmacokinetics and bioavailability of ranitidine in humans. British Journal of Pharmacology 73(1): 275P (1981).Google Scholar
  17. Bohman, T.; Mysen, J. and Larsen, S.: Inhibition of histamine-stimulated gastric secretion in healthy subjects by the H2-receptor antagonists — ranitidine. Scandinavian Journal of Gastroenterology 15: 183 (1980).PubMedGoogle Scholar
  18. Bohnet, H.G. and Riley, A.J.: An investigation of the effect of oral ranitidine treatment on hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal function in male and female volunteers; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.69–76 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  19. Bonfils, S.; Mignon, M.; Vallot, T.H. and Mayeur, S.: Use of ranitidine in the medical treatment of Zollinger-Ellison syndrome. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 119 (1981).Google Scholar
  20. Bovo, P.; Vaona, B.; Angelini, G.; Cavallini, G.; Montesi, G.; Rosa, B. and Scuro, L.A.: Ranitidine and delayed hypersensitivity. Italian Journal of Gastroenterology 15: 49 (1981).Google Scholar
  21. Boyd, E.J.S.; Peden, N.R.; Browning, M.C.K.; Saunders, J.H.B. and Wormsley, K.G.: Clinical and endocrine aspects of treatment with ranitidine. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 81 (1981).Google Scholar
  22. Boyd, E.J.S.; Wilson, J.A.; Peden, N.R. and Wormsley, K.G.: Maintenance treatment of duodenal ulcer with ranitidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 187–189 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  23. Bradshaw, J.; Brittain, R.T.; Clitherow, J.W.; Daly, M.J.; Jack, D.; Price, B.J. and Stables, R.: Ranitidine (AH19065): a new potent selective histamine H2-receptor antagonist. British Journal of Pharmacology 66(3): 46P (1979).Google Scholar
  24. Breen, K.J.; Bury, R.; Desmond, P.V.; Mashford, M.L.; Morphett, B.; Westwood, B. and Shaw, R.G.: Effects of cimetidine and ranitidine on hepatic drug metabolism. Clinical Pharmacology and Therapeutics 31: 297 (1982).PubMedGoogle Scholar
  25. Brittain, R.T.; Daly, M.J. and Sutherland, M.: Ranitidine: An improved H2-receptor antagonist for the treatment of peptic ulcer. Journal of Pharmacy and Pharmacology 32(Suppl. Dec): 76P (1980).Google Scholar
  26. Brogden, R.N.; Heel, R.C.; Speight, T.M. and Avery, G.S.: Cimetidine: A review of its pharmacological properties and therapeutic efficacy in peptic ulcer disease. Drugs 15: 93 (1978).PubMedGoogle Scholar
  27. Broulik, P.D.: Antiandrogen effect of cimetidine in mice. Endokrinologic 76(1): 118 (1980).Google Scholar
  28. Brunner, G.; Losgen, H. and Harke, U.: Ranitidine in the treatment of cimetidine-resistant ulcerations of the upper intestinal tract; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.252–254 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  29. Brynskov, J.; Thyssen, H.H.; Jansen, E. and Munster-Swendsen, J.: Cimetidine and Romberg’s test. Correspondence. Lancet 1: 1421 (1980).PubMedGoogle Scholar
  30. Bunce, K.T.; Clayton, N.M.; Daly, M.J.; Humphray, J.M. and Stables, R.: Protection against aspirin-induced gastric lesions in the rat by the H2-receptor antagonists ranitidine and cimetidine. British Journal of Pharmacology 70(1): 178P (1980).Google Scholar
  31. Burland, W.L.; Duncan, W.A.M.; Hesselbo, T.; Mills, J.G.; Sharpe, P.C.; Haggie, S.J. and Wyllie, J.H.: Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist in healthy man. British Journal of Clinical Pharmacology 2: 481 (1975).PubMedGoogle Scholar
  32. Carey, P.F. and Martin, L.E.: A high performance liquid chromatography method for the determination of ranitidine in plasma. Journal of Liquid Chromatography 2(9): 1291 (1979).Google Scholar
  33. Carey, P.F.; Martin, L.E. and Owen, P.: A method for the determination of ranitidine and its metabolites in urine by h.p.l.c. and its application to study the metabolism and pharmacokinetics of ranitidine in man. Biochemical Society Transactions (1): 112 (1981a).Google Scholar
  34. Carey, P.F.; Martin, L.E. and Owen, P.E.: Determination of ranitidine and its metabolites in human urine by reversed-phase ion-pair high-performance liquid chromatography. Journal of Chromatography 225: 161 (1981b).PubMedGoogle Scholar
  35. Caulin, C.; Isal, J.P.; Alexandre, C.; Simoneau, G. and Tordjman, J.P.: Correlation between intragastric pH and plasma ranitidine concentrations; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.112–116 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  36. Chatterji, A.N.: A double-blind and randomised placebo-controlled study of ranitidine in duodenal ulcer patients. Abstract of paper presented at XIth International Congress of Gastroenterology, Hamburg, June, 1980.Google Scholar
  37. Cockel, R.; Dawson, J. and Jain, S.: Ranitidine in the long-term treatment of gastric ulcers; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.230–236 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  38. Daly, M.J.; Humphray, J.M. and Stables, R.: Antagonism of vasodepressor and gastric secretory responses to histamine by ranitidine and cimetidine in the anaesthetised dog. British Journal of Pharmacology 67(3): 414P (1979a).PubMedGoogle Scholar
  39. Daly, M.J.; Humphray, J.M. and Stables, R.: Inhibition of gastric acid secretion by the new H2-receptor antagonist ranitidine in the dog with a gastric fistula. Gut 20(10): A914 (1979b).Google Scholar
  40. Daly, M.J.; Humphray, J.M. and Stables, R.: Inhibition of gastric acid secretion in the dog by the H2-receptor antagonists, ranitidine, cimetidine and metiamide. Gut 21: 408 (1980).PubMedGoogle Scholar
  41. Daly, M.J. and Stables, R.: In vitro actions of ranitidine, a new histamine H2-receptor antagonist. Agents and Actions 10: 190 (1980).PubMedGoogle Scholar
  42. Daly, M.; Stables, R.; Bell, J.A. and Manchee, G.R.: Simultaneous measurement of gastric mucosal blood flow by the 3H-aniline and 14C-aminopyrine clearance methods in the conscious Heidenhain pouch dog; in Fielding (Ed.) Gastrointestinal Mucosal Blood Flow, pp.94–104 (Churchill Livingstone, Edinburgh 1980).Google Scholar
  43. Daly, M.J.; Humphray, J.M. and Stables, R.: Some in vitro and in vivo actions of the new histamine H2-receptor antagonist, ranitidine. British Journal of Pharmacology 72: 49 (1981a).PubMedGoogle Scholar
  44. Daly, M.J.; Humphray, J.M.; Bunce, K.T. and Stables, R.: The effect of ranitidine on gastric acid secretory response curves to histamine, pentagastrin, or bethanechol in the dog with a Heidenhain Pouch. Agents and Actions 11: 160 (1981b).PubMedGoogle Scholar
  45. Daly, M.J.; Humphray, J.M. and Stables, R.: Antagonism of vasodepressor and gastric secretory responses to histamine by the H2-receptor antagonists ranitidine and cimetidine in the anaesthetised dog. British Journal of Pharmacology 72: 55 (1981c).PubMedGoogle Scholar
  46. Dansmann, H.G. and Simon, B.: The new histamine H2-receptor antagonist ranitidine. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 39 (1981).Google Scholar
  47. Danilewitz, M.; Tim, L.O. and Hirschomitz, B.: Ranitidine suppression of gastric hypersecretion resistant to cimetidine. New England Journal of Medicine 306: 20 (1982).PubMedGoogle Scholar
  48. Dawson, J and Cockel, R.: Ranitidine in acute upper gastrointestinal haemorrhage. Scandinavian Journal of Gastroenterology 17(Suppl. 78): 212 (1982a).Google Scholar
  49. Dawson, J. and Cockel, R.: Ranitidine in acute upper gastrointestinal haemorrhage. B.M.J. 285: 476–477 (1982b).Google Scholar
  50. Delitala, G.; Devilla, L.; Pende, A. and Lotti, G.: Stimulation of prolactin induced by ranitidine, an antagonist of histamine H2-receptors in man. Journal of Endocrinology. Invest 3(Suppl. 1): 12 (1980).Google Scholar
  51. Delle Fave, G.F.; Tamburrano, G.; De Magistris, L.; Natoli, C.; Santoro, M.L.; Carratu, R. and Torsoli, A.: Gynaecomastia with cimetidine. Lancet 1: 1319 (1977).Google Scholar
  52. Desmond, P.V.; Patwardhan, R.V.; Schenker, S. and Speeg, K.V.: Cimetidine impairs elimination of chlordiazepoxide (Librium) in man. Annals of Internal Medicine 93: 266 (1980).PubMedGoogle Scholar
  53. Desmond, P.V.; Shaw, R.G.; Bury, R.W.; Mashford, M.L. and Breen, K.J.: Cimetidine impairs the clearance of an orally administered high clearance drug, chlormethiazide. Gastroenterology 80: 1330 (1981).Google Scholar
  54. Dixon, G.T.; Fowler, P.A. and Maconochie, J.G.: Preclinical volunteer studies with ranitidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Symposium Series 5, pp.11–17 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  55. Dobrilla, G.; de Pretis, G.; Felder, M. and Chilovi, F.: Endoscopic double-blind controlled trial of ranitidine vs placebo in the short term treatment of duodenal ulcer. Hepato-Gastroenterology 28: 49 (1981a).PubMedGoogle Scholar
  56. Dobrilla, G.; Barbar, L.; Bianchi Porro, G.; Felder, M.; Mazzacca, G.; Miglioli, L.; Pera, A.; Petrillo, M.; Sabbatini, F. and Verme, G.: Placebo controlled with ranitidine in duodenal ulcer. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 101 (1981b).Google Scholar
  57. Domschke, W.; Lux, G. and Domschke, S.: Furan H2-antagonist ranitidine inhibits pentagastrin-stimulated gastric secretion stronger than cimetidine. Gastroenterology 79: 1267 (1980).PubMedGoogle Scholar
  58. Durrant, J.M. and Strunin, L.: Comparative trial of ranitidine, cimetidine and a placebo on gastric secretion in fasting patients at induction of anaesthesia; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.308–312 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  59. Edwards, C.R.W. and Riley, A.J.: Endocrine effects of ranitidine: comparison with cimetidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.64–68 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  60. Edwards, C.R.W.; Yeo, T.; Delitala, G.; Al Dujaili, E.A.S.; Boscaro, M. and Besser, G.M.: In vitro studies on the effects of ranitidine on isolated anterior pituitary and adrenal cells. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 75 (1981).Google Scholar
  61. Eshelman, F.N.; Gorg, D.C. and Widler, D.J.: Clinical pharmacokinetics of ranitidine following multiple dose administration intravenously. Drug Intelligence and Clinical Pharmacy 15(6): 478 (1981).Google Scholar
  62. Feeley, J. and Guy, E.: Ranitidine also reduces liver blood flow. Lancet 1: 169 (1982).PubMedGoogle Scholar
  63. Festen, H.P.M.; Diemel, J.; Lamers, C.B.H.; Van Schaik, A.; Tangerman, A. and Van Tongeren, J.H.M.: Is the measurement of blood cimetidine levels useful. British Journal of Clinical Pharmacology 12: 417 (1981).PubMedGoogle Scholar
  64. Francis, R.N. and Kim, R.S.H.: Oral ranitidine for prophylaxis against Mendelson’s Syndrome. Anesthesia and Analgesia 61: 103 (1982).Google Scholar
  65. Funder, J.W. and Mercer, J.E.: Cimetidine, a histamine H2-receptor antagonist, occupies antrogen receptors. Journal of Clinical Endocrinology and Metabolism 48: 189 (1979).PubMedGoogle Scholar
  66. Galmiche, J.P.; Desechalliers, J.P.; Denis, P.; Chevallier, B. and Colin, R.: Ranitidine treatment of cimetidine-resistant peptic ulcers: preliminary clinical and 24-hour intragastric acidity results; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.241–248 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  67. Garg, D.C.; Weidler, D.J.; Baltodano, N. and Eshelman, F.N.: Pharmacokinetics of ranitidine, a new histamine H2-receptor blocker. Abstract. Clinical Pharmacology and Therapeutics 29: 248 (1981).Google Scholar
  68. Gibinski, K.; Nowak, A.; Gabryelewicz, A.; Szalaj, W.; Hasik, J.; Klincewicz, H.; Pokora, J.; Radwan, P.; Kosecki, P. and Pachlewski, J.: Multicentre double blind clinical trial on ranitidine for gastro-duodenal ulcer. Hepatogastroenterology 28: 216 (1981).PubMedGoogle Scholar
  69. Gibinski, K.; Nowak, A.; Gabryelewicz, A.; Szalaj, W.; Hasik, J.; Klimcewicz, H.; Pokora, J.; Radwan, P.; Kosecki, P.; Pachlewski, J.; Butruk, E. and Ruzyllo, E.: Treatment of duodenal and gastric ulcer with ranitidine: a controlled multicentre clinical trial; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 170–175 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  70. Gough, K.: Different doses of ranitidine in the long-term treatment of duodenal ulcer: interim analysis; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 194–198 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  71. Grahnen, A.; von Bahr, C.; Lindstrom, B. and Rosen, A.: Bioavailability and pharmacokinetics of cimetidine. European Journal of Clinical Pharmacology 16: 335 (1979).PubMedGoogle Scholar
  72. Gugler, R.; Fuchs, G.; Dieckmann, M. and Somogyi, A.A.: Cimetidine plasma concentration-response relationships. Clinical Pharmacology and Therapeutics 29: 744 (1981).PubMedGoogle Scholar
  73. Guslandi, M.; Baltarin, E. and Tittobello, A.: Gastric mucus secretion in ranitidine treated patients. British Medical Journal 283: 699 (1981).PubMedGoogle Scholar
  74. Guslandi, M.; Testoni, P.A.; Fesce, E.; Baltarin, E. and Tittobello, A.: Behaviour of gastric mucin during pirenzepine treatment: A double-blind controlled study versus cimetidine. Current Therapeutic Research 27: 714 (1980).Google Scholar
  75. Hagenmuller, F.; Zeitler-Abu-Ishira, A. and Classen, M.: Inhibition of gastric acid secretion by the new histamine H2-receptor antagonist AH19065 (ranitidine) and cimetidine. A double-blind trial. Gut 20(10):A905 (1979).Google Scholar
  76. Hall, W.H.: Breast changes in males on cimetidine. New England Journal of Medicine 295: 841 (1976).PubMedGoogle Scholar
  77. Halloran, L.G.; Zeass, A.M.; Gayle, W.E.; Wheeler, C.B. and Miller, D.J.: Prevention of acute gastrointestinal complications after severe head injury: A controlled trial of cimetidine prophylaxis. American Journal of Surgery 139: 44–48 (1980).PubMedGoogle Scholar
  78. Halparin, L. and Reudy, J.: Inhibition of pentagastrin-stimulated gastric acid secretion by ranitidine hydrochloride and cimetidine. Current Therapeutic Research 28: 154 (1980).Google Scholar
  79. Hanson, R.G.; Mihaly, G.W.; Smallwood, R.A.; Louis, W.J. and Yeomans, N.D.: The inhibition of gastric acid secretion by ranitidine: The effect of 6 weeks ranitidine therapy. Abstract. Gastroenterology 80 (5, Part 2): 1168 (1981).Google Scholar
  80. Henry, D.A. and Langman, M.J.S.: The effects of H2-receptor antagonists on hepatic drug metabolism. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 85 (1981).Google Scholar
  81. Henry, D.A.; MacDonald, I.A.; Kitchingman, G.; Bell, G.D. and Langman, M.J.S.: Cimetidine and ranitidine: comparison of effects on hepatic drug metabolism. British Medical Journal 281: 775 (1980).PubMedGoogle Scholar
  82. Hetzel, D.J.; Bochner, F.; Hallpike, J.F. and Shearman, D.J.C.: Cimetidine interaction with phenytoin. British Medical Journal 282: 1512 (1981).PubMedGoogle Scholar
  83. Humphray, J.M.; Daly, M.J. and Stables, R.: Effects of ranitidine and cimetidine on gastric and salivary secretion induced by bethanechol in the anaesthetised dog. Gut 21(10): A930 (1980).Google Scholar
  84. Hunt, R.H.; Walt, R.P.; Trotman, I.F.; Colley, S.; Bewar, E.P.; Frost, R.A.; Shepherd, T.H.; Golding, P.L.; Colin-Jones, D.G.; Misiewicz, J.J. and Milton-Thompson, G.J.: Comparison of ranitidine, 150mg nocte, with cimetidine, 400mg nocte, in the maintenance treatment of duodenal ulcer; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 190–193 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  85. Jansen, E.C.; Brynskov, J. and Thyssen, H.H.: Influence of ranitidine on postural stability. Correspondence. Lancet 1: 55 (1982).PubMedGoogle Scholar
  86. Jones, D.B.; Rose, J.D.R.; Smith, P.M. and Calcraft, B.J.: Treatment of peptic ulcer with ranitidine — a clinical trial; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 183–186 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  87. Kett, K.; Aadland, E and Berstad, A.: Inhibition of gastric secretion in man with a new H2-receptor antagonist, ranitidine. Scandinavian Journal of Gastroenterology 15: 249 (1980).PubMedGoogle Scholar
  88. Klotz, U. and Reimann, I.: Delayed clearance of diazepam due to cimetidine. New England Journal of Medicine 302: 1012 (1980).PubMedGoogle Scholar
  89. Klotz, U. and Reimann, I.: Influence of ranitidine on the disposition of low and high clearance drugs in man; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.95–101 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  90. Konturek, S.J.; Kwiecien, N.; Obtulowicz, W. and Oleksy, J.: Cytoprotective effects of ranitidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 121–126 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  91. Konturek, S.J.; Obtulowicz, W.; Kwiecien, N.; Sito, E.; Mikos, E. and Oleksy, J.: Comparison of ranitidine and cimetidine in the inhibition of histamine, sham feeding and meal induced gastric secretion in duodenal ulcer patients. Gut 21: 181 (1980a).PubMedGoogle Scholar
  92. Konturek, S.J.; Obtulowicz, W.; Kwiecien, N.; Sito, E.; Oleksy, J. and Miszezuk-Jamska, B.: Effect of ranitidine, a new H2-antagonist, on gastric and pancreatic secretion in duodenal ulcer patients. Digestive Diseases and Sciences 25: 737 (1980b).PubMedGoogle Scholar
  93. Konturek, S.J.; Obtulowicz, W.; Kwiecien, N.; Kopp, B. and Oleksy, J.: Kinetics and duration of action of ranitidine on gastric secretion and its effect on pancreatic secretion in duodenal ulcer patients. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 91 (1981a).Google Scholar
  94. Konturek, S.J.; Obtulowicz, W.; Kwiecien, N.; Kopp, B. and Olesky, J.: Dynamics of gastric acid inhibition by ranitidine in duodenal ulcer patients. Digestion 22: 119 (1981b).PubMedGoogle Scholar
  95. Konturek, S.J.; Radecki, T.; Brzozowski, T.; Piastucki, I.; Dembinska-Kiec, A. and Zmida, A.: Gastric cytoprotection by prostaglandins, ranitidine and probanthine in rats. Role of endogenous prostaglandins. Scandinavian Journal of Gastroenterology 16: 7 (1981c).PubMedGoogle Scholar
  96. Korman, M.G.; Hansky, J.; Merrett, A.C. and Schmidt, G.T.: Ranitidine in duodenal ulcer: Healing rate and effect of smoking. Abstract. Gastroenterology 80 (5, part 2): 1197 (1981).Google Scholar
  97. Langman, M.J.S.; Henry, D.H.; Bell, G.D.; Burnham, W.R. and Ogilvy, A.: Cimetidine and ranitidine in duodenal ulcer. British Medical Journal 281: 473 (1980).PubMedGoogle Scholar
  98. Langman, M.J.S.; Henry, D.A. and Ogilvie, A.: Ranitidine and cimetidine for duodenal ulcer. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 115 (1981).Google Scholar
  99. Laverdant, C.; Vergeau, B.; Molinie, C.; Essioux, H.; Daly, J.P. and Pappo, B.: La ranitidine, nouvel antagoniste des recepteurs H2 de l’histamine, dans de traitement de l’ulcere duodenal. Medecine et Armees 8: 623 (1980).Google Scholar
  100. Lebert, P.A.; MacLeod, S.M.; Mahon, W.A.; Soldin, S.J. and Vandenberghe, H.M.: Ranitidine kinetics and dynamics. I. Oral dose studies. Clinical Pharmacology and Therapeutics 30: 539 (1981a).PubMedGoogle Scholar
  101. Lebert, P.A.; Mahon, W.A.; MacLeod, S.M.; Soldin, S.J.; Fenje, P. and Vandenberghe, H.M.: Ranitidine kinetics and dynamics. II. Intravenous dose studies and comparison with cimetidine. Clinical Pharmacology and Therapeutics 30: 545 (1981b).PubMedGoogle Scholar
  102. Lee, F.I.; Costello, F.T. and Fielding, J.D.: Ranitidine compared with placebo in the short-term healing of duodenal ulcer; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 129–133 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  103. Lim, C.G.; Forster, J.K.; Jackson, J.L.; Robinson, W.D. and Tracey, L.E.: Ranitidine in duodenal ulcer: An international collaborative study. Abstract. Gastroenterology 80 (5, part 2): 1214 (1981).Google Scholar
  104. Lishman, A.H. and Record, CO.: Ranitidine in the management of duodenal ulceration: Controlled and open comparison with cimetidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 161–165 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  105. Lohrmann, A.; Hotz, J.; Eysselein, V.; Singer, M.V. and Goebell, H.: Effects of intraduodenal administration of ranitidine and cimetidine on secretion of gastric acid, pepsin, gastrin and pancreatic polypeptides in man. Gastroenterology 78: 1210 (1980)Google Scholar
  106. Lombardo, L.: Reversible amenorrhoea after ranitidine treatment. Correspondence. Lancet 1: 224 (1982).PubMedGoogle Scholar
  107. Londong, W.; Londong, V.; Ruthe, C. and Weizert, P.: Complete inhibition of food-stimulated gastric acid secretion by combined application of pirenzepine and ranitidine. Gut 22: 542 (1981).PubMedGoogle Scholar
  108. Louis, W.J.; Mihaly, G.W.; Hanson, R.G.; Anderson, A.; McNeil, J.J.; Yeomans, N.D. and Smallwood, R.A.: Pharmacokinetics and gastric secretory studies of ranitidine in man. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 11 (1981).Google Scholar
  109. McCallum, R.W.; Kuljian, B.; Laborny, B. and Eshelman, F.: Inhibition of pentagastrin-stimulated gastric acid secretion with intravenous ranitidine: A comparison to cimetidine. Abstract. Gastroenterology 80 (5, part 2): 1226 (1981).Google Scholar
  110. Macchi, H.; Fiasse, R.; Reynaert, M.; Desager, J.P. and Dive, Ch.: Effect of intravenous ranitidine on gastric acid secretion in severely ill patients admitted to an intensive care unit; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.267–272 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  111. MacDougall, B.R.D.; Bailey, R.J. and Williams, R.: H2-receptor antagonists and antacids in the prevention of acute gastrointestinal haemorrhage in fulminant hepatic failure: Two controlled trials. Lancet 1: 617–619 (1977).PubMedGoogle Scholar
  112. McElwee, H.P.; Sirinek, K. and Levine, B.A.: Cimetidine affords protection equal to antacids in prevention of stress ulceration following thermal injury. Surgery 86: 620–626 (1979).PubMedGoogle Scholar
  113. McFadyen, M.L.; Folf, P.I.; Marks, I.N.; Wright, J.P. and Lucke, W.: The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration. Scandinavian Journal of Gastroenterology 16(Suppl. 69). 109 (1981).Google Scholar
  114. McGonigle, R.J.S.; Williams, L.C.; Amphlett, G.E.; England, R.J. and Parsons V.: The pharmacokinetics of ranitidine in renal disease; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.41–46 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  115. McGregor, C.G.A.; Ogg, L.J.; Smith, I.S.; Cochran, A.J.; Gray, G.R.; Gillespie, G.; Forrester, J.: Immunological and other laboratory studies of patients receiving short term cimetidine therapy. Lancet 1: 122–123 (1977).PubMedGoogle Scholar
  116. Mackay, C.; Mohammed, R.; Lee, F.I.; Fielding, J.D.; Holmes, G.K.T. and Hine, K.: The effect of ranitidine, a new histamine H2-receptor antagonist on the healing rate of duodenal ulceration. Abstract. Gastroenterology 80 (5, part 2): 1219 (1981).Google Scholar
  117. McNeil, J.J.; Mihaly, G.W.; Anderson, A.; Marshall, A.W.; Smallwood, R.A. and Louis, W.J.: Pharmacokinetics of the H2-receptor antagonist ranitidine in man. British Journal of Clinical Pharmacology 12: 411 (1981).PubMedGoogle Scholar
  118. Mahon, W.A.; Macleod, P.A.; Lebert, S.J. and Soldin, S.J.: Ranitidine vs cimetidine: Effects on pentagastrin-stimulated gastric acid and pepsin. Abstract 73 of paper presented at the World Conference on Clinical Pharmacology and Therapeutics London, August, 1980.Google Scholar
  119. Majumdar, S.K.; Thompson, A.D. and Shaw G.K.: Cimetidine and serum prolactin. British Medical Journal 1: 409 (1978).PubMedGoogle Scholar
  120. Marks, I.N.; Wright, J.P.; Denyer, M.; Hatfield, A.; Girdwood, A.H. and Lucke, W.: Ranitidine heals duodenal ulcers. South African Medical Journal 61: 152 (1982).PubMedGoogle Scholar
  121. Martin, L.E.; Bell, J.A.; Carey, P.F.; Dallas, F.A.A.; Dixon, G.T. and Jenner, W.N.: A review of pharmacokinetics and metabolism of ranitidine in animals and man; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.23–31 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  122. Masala, A.; Alagna, S.; Faedda, R.; Satta, A. and Rovasio, P.P.: Prolactin secretion in man following acute and long term cimetidine administration. Acta Endocrinologica 93: 392 (1980).PubMedGoogle Scholar
  123. Mayersohn, M.: Physiological factors that modify systemic drug availability and pharmacologic response in clinical practice; in Blanehard et al. (Eds) Principles and Perspectives in Drug Bioavailability, pp.211–273 (Karger, Basel 1979).Google Scholar
  124. Merrett, A.C.; Hansky, J.; Korman, M.G. and Schmidt, G.T.: Ranitidine in duodenal ulcer: Healing rate and effect of smoking. Australian and New Zealand Journal of Medicine 12: 107 (1982).Google Scholar
  125. Mignon, M.; Savage, M.; Le Roux, S. and Bonfils, S.: Effect de doses varieés de ranitidine sur la secretion acide la vidange gastrique et la gastrine serique lors d’un repas test chez l’homme. Gastro-Enterologie Clinique et Biologique 4:(IBIS) 158A (1980).Google Scholar
  126. Mignon, M.; Vallot, T. and Bonfils S.: Use of ranitidine in the management of Zollinger-Ellison syndrome; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.279–280 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  127. Mignon, M.; Vallot, T.H.; Mayeur, S. and Bonfils, S.: Ranitidine and cimetidine in Zollinger-Ellison syndrome. Letter to the Editor. British Journal of Clinical Pharmacology 10: 173–174 (1980).PubMedGoogle Scholar
  128. Mignon, M.; Vallot, T.; Mayeur, S.; Treffot, M.-J. and Bonfils, S.: Interet d’un nouvel antagoniste de recepteurs H2, la ranitidine, dans le traitément du syndrome de Zollinger-Ellison. Gastroenterologie Clinique et Biologique 5: 42 (1981).PubMedGoogle Scholar
  129. Mihaly, G.W.; Drummer, O.H.; Marshall, A.; Smallwood, R.A. and Louis, W.J.: High pressure liquid chromatographic determination of ranitidine, a new H2-receptor antagonist, in plasma and urine. Journal of Pharmaceutical Sciences 69: 1155 (1980a).PubMedGoogle Scholar
  130. Mihaly, G.W.; Morgan, D.J.; Marshall, A.W.; Cockbain, S.; Smallwood, R.A. and Hardy, K.J.: Placental transfer of the H2-receptor antagonist ranitidine. Abstract of paper presented at the 14th Annual Meeting of the Australasian Society of Clinical and Experimental Pharmacologists (ASCEP) Dec, 1980b.Google Scholar
  131. Mohammed, R.; Clark, J.S.; Adams, J.F.; Hearns, J.B. and Crean, G.P.: The effect of ranitidine hydrochloride, a new histamine H2-receptor antagonist, on intrinsic factor secretion. Clinical Therapeutics 4(2): 118 (1981).PubMedGoogle Scholar
  132. Mohammed, R.; Mitchell, K.G. and Mackay, C.: The treatment of ‘cimetidine resistant’ peptic ulcers by ranitidine hydrochloride: A new histamine H2-receptor antagonist. Current Medical Research and Opinion 7: 523 (1981).PubMedGoogle Scholar
  133. Mohammed, R.; Mitchell, K. and MacKay, C.: The treatment of cimetidine-resistant peptic ulcers with ranitidine hydrochloride; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.249–251 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  134. Morgan, A.G.; McAdam W.A.F. and Pacsoo, C.: A comparison of ranitidine with Caved-S in duodenal ulcer treatment; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 166–169 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  135. Moshal, M.G.; Spitaels, J.M. and Khan, F.: A double-blind endoscopically controlled trial of ranitidine in a high incidence area. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 129 (1981a).Google Scholar
  136. Moshal, M.G.; Spitaels, J.M. and Kahn, F.: Ranitidine in uncomplicated duodenal ulceration. South African Medical Journal 60: 393 (1981b).PubMedGoogle Scholar
  137. Muller-Lissner, S.A.; Sonnenberg, A.; Eichenberger, P. and Blum, A.L.: Effect of ranitidine on gastric acid and pepsin secretion following sham feeding. Scandinavian Journal of Gastroenterology 16(Suppl. 69): 27 (1981).Google Scholar
  138. Nelis, G.F.: Controlled trial with ranitidine in the treatment of peptic ulcer. Netherlands Journal of Medicine 24: 224 (1981).PubMedGoogle Scholar
  139. Nowak, A.; Gibiński, K.; Saliński, C.Z.; Górka, Z.; Nowakowska, E. and Rudzki, J.: Ranitidine in the medical management of acute upper gastrointestinal bleeding; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.255–260 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  140. Nowak, A.; Sadlinski, C.Z.; Górka, Z.; Nowakowska, E.; Rudzki, J. and Gibiński, K.: Ranitidine in the treatment of acute upper gastrointestinal haemorrhage. A comparative study. Hepato-Gastroenterology 28: 267 (1981).PubMedGoogle Scholar
  141. Okabe, S. and Kawakami, M.: Effects of ranitidine, a new histamine H2-receptor antagonist, on secretagogue-stimulated gastric secretion in rats: Comparison with cimetidine. Folia Pharmacologica Japonica 78: 54 (1981).Google Scholar
  142. Okabe, S.; Kunimi, H. and Ohtsuki, H.: Effects of a new histamine H2 receptor antagonist, ranitidine, on experimental acute gastric and duodenal ulcers. Folia Pharmacologica Japonica 77: 397 (1981).PubMedGoogle Scholar
  143. Okabe, S. and Tabata, K.: Effects of histamine H2-receptor antagonists, ranitidine and cimetidine, on aspirin-induced gastric lesions in rats and dogs. Abstract. Gastroenterology 80(5, part 2): 1242 (1981).Google Scholar
  144. Paré, P; Lev́esque, D; Archambault, A; Farley, A; Gosselin, D; Leroux, P; Pilon, G; Sherbaniuk, R; Trautman, A and Thomson, A.B.R.: Effect of ranitidine on healing of peptic ulcer; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 178–182 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  145. Pasquali, R.; Corinaldesi, R.; Miglioli, M.; Melchionda, A.; Capelli, M. and Barbara, L.: Effect of prolonged administration of ranitidine on pituitary and thyroid hormones, and their response to specific hypothalamic-releasing factors. Clinical Endocrinology 15: 457 (1981).PubMedGoogle Scholar
  146. Patuardham, R.V.; Yarborough, G.W.; Desmond, P.V.; Johnson, R.F.; Schenker, S. and Speeg, K.V.: Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology 79: 912 (1980).Google Scholar
  147. Pearce, P. and Funder, J.W.: Histamine H2-receptor antagonist: radioreceptor assay for antiandrogen side effects. Clinical and Experimental Pharmacology and Physiology 7: 442 (1980).Google Scholar
  148. Peden, N.R.; Boyd, E.J.S.; Browning, M.C.K.; Saunders, J.H.B. and Wormsley, K.G.: Effects of two histamine H2-receptor blocking drugs on basal levels of gonadotrophins, prolactin, testosterone and oestradiol-17B during treatment of duodenal ulcer in male patients. Acta Endocrinologica 96: 564 (1981a).PubMedGoogle Scholar
  149. Peden, N.R.; Boyd, E.J.S.; Saunders, J.H.B. and Wormsley, K.G.: Ranitidine in the treatment of duodenal ulceration. Scandinavian Journal of Gastroenterology 16: 325 (1981b).PubMedGoogle Scholar
  150. Peden, N.R.; Richards, D.A.; Saunders, J.H.B. and Wormsley, K.G.: Pharmacologically effective plasma concentrations of ranitidine. Correspondence. Lancet 2: 199–200 (1979).PubMedGoogle Scholar
  151. Peden, N.R.; Saunders, J.H.B. and Wormsley, K.G.: Inhibition of pentagastrin-stimulated and nocturnal gastric secretion by ranitidine. Lancet 1: 690 (1979).PubMedGoogle Scholar
  152. Pedersen, P.V.: Pharmacokinetic analysis by linear system approach I: Cimetidine bioavailability and second peak phenomenon. Journal of Pharmaceutical Sciences 70: 32 (1981).Google Scholar
  153. Poro, G.B.; Petrillo M. and Lazzaroni M.: Ranitidine in the short-term treatment of duodenal ulcer: a multicentre endoscopic double-blind trial; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 134–144 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  154. Poynter, D.; Pick, C.R.; Harcourt, R.A.; Sutherland, M.F.; Spurling, N.W.; Ainge, G.; Cook, J. and Gatehouse, D.: Evaluation of ranitidine safety; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.48–56 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  155. Puurunen, J.; Sotaniemi, E. and Pelkonen, O.: Effect of cimetidine on microsomal drug metabolism in man. European Journal of Pharmacology 18: 185 (1980).Google Scholar
  156. Quina, M.: Clinical trial of ranitidine in duodenal ulcer in Portugal; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 176–177 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  157. Rendić, S.; Alebić-Kolbah, T.; Kajtez, F. and Ruf, H.-H.: Interaction of ranitidine with liver enzymes. Xenobiotica 12: 9 (1982).PubMedGoogle Scholar
  158. Rendić, S.; Sunjić, V.; Toso, R. and Kajbez, F.: Interaction of cimetidine with liver enzymes. Xenobiotica 9: 555 (1979).PubMedGoogle Scholar
  159. Riley, A.J.; Crowley, P. and Harrison, C.: Transfer of ranitidine to biological fluids: milk and semen; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.77–86 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  160. Roberts, D.M.; Wilson, J.A.; Ratcliffe, G.E.; Waring, A.J.; Reilly, M.J. and Lloyd, J.S.: Clinical trial of ranitidine in the treatment of peptic ulcer. British Journal of Clinical Practice 36: 9 (1982).PubMedGoogle Scholar
  161. Roberts, R.K.; Grice, J.; Wood, L; Petroft, V. and McGuffie, C.: Cimetidine impairs the elimination of theophylline and antipyrine. Gastroenterology 81: 19 (1981).PubMedGoogle Scholar
  162. Robins, A.H. and McFadyen, M.L.: Effect of the new H2-receptor antagonist ranitidine on plasma prolactin levels in duodenal ulcer patients. Journal of Pharmacy and Pharmacology 33: 615 (1981).PubMedGoogle Scholar
  163. Ryan, F.P.: A comparison of ranitidine and placebo in the acute treatment of gastric ulcer; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 199–203 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  164. Serlin, M.J.: Ranitidine and cimetidine: interactions with other drugs; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.87–94 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  165. Serlin, M.J.; Sibeon, R.G.; Mossman, S.; Breckenridge, A.W.; Williams, J.R.B.; Atwood, J.L. and Willoughby, J.M.T.: Cimetidine: Interaction with oral anticoagulants in man. Lancet 2: 317 (1979).PubMedGoogle Scholar
  166. Serlin, M.J.; Sibeon, R.G. and Breckenridge, A.M.: Lack of effect of ranitidine on warfarin action. British Journal of Clinical Pharmacology 12: 791 (1981).PubMedGoogle Scholar
  167. Sewing, K-Fr.: Pharmacodynamics and pharmacokinetics of ranitidine in man; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.32–40 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  168. Sewing, K-Fr.; Billian, A.; Malchow, H.: Comparative study with ranitidine and cimetidine on gastric secretion in normal volunteers. Gut 21: 750 (1980).PubMedGoogle Scholar
  169. Sharpe, P.C. and Hawkins, B.W.: Efficacy and safety of cimetidine. Long term treatment with cimetidine; in Burland and Simkins (Eds) Cimetidine p.358 (Excerpta Medica, Amsterdam 1977).Google Scholar
  170. Sheers, R. and Roberts, N.: The effect of ranitidine and cimetidine on pentagastrin and insulin stimulated gastric secretion. Scandinavian Journal of Gastroenterology 16(Suppl 69): 51 (1981).Google Scholar
  171. Sheers, R.; McKay, J.S. and Hughes, S.: Ranitidine and duodenal ulceration: A short term and maintenance study. Journal of the Royal Society of Medicine 75: 323 (1982).PubMedGoogle Scholar
  172. Sheers, R. and Roberts N.B.: Ranitidine and pepsin secretion; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 117–120 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  173. Sherbaniuk, R.; Wensel, R.; Trautman, A.; Grace, M.; Kirdeikis, P.; Jewell, L.; Paré, P.; Lévesque, D.; Farley, A.; Archambault, A. and Thomson A.B.R.: Ranitidine in the short-term management of symptomatic gastro-oesophageal reflux; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.281–290 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  174. Simon, B.; Muller, P.; Dammann, H-G.; Kommerell, B.: Adverse effects of cimetidine and safety profile of ranitidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.57–63 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  175. Socha, J.; Rondio, H.; Chaba Celinska, D.; Rasinski, A.; and Bogoniowska, Z.: Ranitidine treatment of peptic and related diseases in children; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.303–307 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  176. Somogyi, A. and Gugler, R.: Drug interactions with cimetidine. Clinical Pharmacokinetics 7: 23 (1982).PubMedGoogle Scholar
  177. Sonne, J.; Poulsen, H.E.; DØssing, M.; Larsen, N.E. and Andreasen, P.B.: Cimetidine clearance and bioavailability in hepatic cirrhosis. Clinical Pharmacology and Therapeutics 29: 191 (1981).PubMedGoogle Scholar
  178. Spiegel, A.M.; Lopatin, R.; Peiken, S. and McCarthy, D.: Serum prolactin in patients receiving chronic oral cimetidine. Lancet 1: 881 (1978).PubMedGoogle Scholar
  179. Stables, R. and Daly, M.J.: Inhibition of gastric acid secretion in the dog by the histamine H2-receptor antagonists ranitidine and cimetidine. Agents and Actions 10: 191 (1980).PubMedGoogle Scholar
  180. Staiger, Von C.; Simon, B.; de Vries, J.; Kather, H. and Walter, E.: Untersuchurgen zur Wirkung von Rantidin auf den Antipyrin-metabolism. Zeitschrift für Gastroenterologie 18: 601 (1980).PubMedGoogle Scholar
  181. Takemoto, T.; Okita, K.; Namiki, M; Ishikawa, M. and Oshiba S.: Clinical studies on gastric ulcer in Japan — pilot and extended open studies; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.220–229 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  182. Takenioto, T.; Okazaki, Y.; Okita, K.; Namiki, M.; Ishikawa, M.; Oshiba, S. and Kurokawa, K.: Ranitidine: A pilot trial in Japan. Scandinavian Journal of Gastroenterology 16(Supp. 69): 125 (1981).Google Scholar
  183. van den Berg, B. and van Blankenstein, M.: The prevention of stress-induced upper gastrointestinal bleeding by ranitidine in critically ill patients; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.261–266 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  184. van Dommelen, C.K.V.; Stadler, F.H. and Boekhorst, J.C.: Comparison of ranitidine with cimetidine in the treatment of duodenal ulcer; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 152–154 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  185. Vieira, M.R.; Godinho, F.; Tavares, J. and Correia, J.P.: Double-blind, cross-over comparison of the effects of ranitidine and cimetidine on hepatic drug metabolism in healthy volunteers; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 102–106 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  186. Von Kleist, D.; Graf, K.J.; Dougherty, F.C. and Hampel, K.E.: Effects of cimetidine and ranitidine on gastric transmural potential difference and on prolactin secretion in man. Hepatogastroenterology 28: 210 (1980).Google Scholar
  187. Walkenstein, S.S.; Dubb, J.W.; Randolph, W.C.; Westlake, W.J.; State, R.M. and Intoccia, A.P.: Bioavailability of cimetidine in man. Gastroenterology 74: 360 (178).Google Scholar
  188. Walt, R.P.; Price, D.K.; Rawlings, J.; Hunt, R.H.; Milton-Thompson, G.J. and Misiewicz, J.J.: Is ranitidine longer-acting than cimetidine. Gut 21(10): A898 (1980).Google Scholar
  189. Walt, R.D.; Malé, P-J.; Rawlings, J.; Hunt, R.H.; Milton-Thompson, G.J. and Misiewicz, J.J.: Comparison of the effects of ranitidine, cimetidine and placebo on the 24 hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer. Gut 22: 49 (1981a).PubMedGoogle Scholar
  190. Walt, R.D.; Male, P-J.; Hunt, R.H.; Rawlings, J.; Milton-Thompson, G.J. and Misiewicz, J. J.: The effect of ranitidine and cimetidine on the twenty-four hour intragastric acidity profile and nocturnal acid secretion in duodenal ulcer patients. Scandinavian Journal of Gastroenterology 16(Supp. 69): 33 (1981b).Google Scholar
  191. Walt, R.P.; La Brooy, S.J.; Avgerinos, A.; Oehr, T.; Riley, A. and Misiewicz, J.J.: Investigation on the penetration of ranitidine into the cerebrospinal fluid and a comparison of the effects of ranitidine on male sex hormones. Scandinavian Journal of Gastroenterology 16(Suppl. 60): 19 (1981c).Google Scholar
  192. Walt, R.P.; Trotman, I.F.; Frost, R.; Golding, P.L.; Shepherd, T.H.; Rawlings, J.; Hunt, R.H.; Colin-Jones, D.; Milton-Thompson G.J. and Misiewicz, J.J.: Comparison of twice daily ranitidine with standard cimetidine treatment of duodenal ulcer. Gut 22: 319 (1981d).PubMedGoogle Scholar
  193. Webster, J.; Barber, H.E.; Hawksworth, G.M.; Jeffers, T.A.; Petersen, J.; Petrie, J.C.; Brunt, P.W.; Mowat, N.A.G. and Griffiths, R.: Cimetidine — A Clinical and pharmacokinetic study. British Journal of Clinical Pharmacology 11: 333 (1981).PubMedGoogle Scholar
  194. Wesdorp, I.C.E.; Dekker, K. and Klinkenberg-Knol, E.: Evaluation of ranitidine in the treatment of reflux oesophagitis; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.291–294 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  195. Witzel, L. and Wolbergs, E.: Effect of ranitidine on ulcer healing. Abstract. Gastroenterology 80 (5, Part 2): 1318 (1981).Google Scholar
  196. Woodings, E.P.; Dixon, G.T.; Harrison, C.; Carey, P. and Richards, D.A.: Ranitidine — a new H2-receptor antagonist. Gut 21: 187 (1980).PubMedGoogle Scholar
  197. Wright, J.P.; Marks, I.N.; Mee, A.S.; Girdwood, H.A.; Bornman, P.C.; Gilinksy, N.H.; Tobias, P. and Lucke, W.: Ranitidine in the treatment of gastric ulceration. South African Medical Journal 61: 155 (1981).Google Scholar
  198. Wright, J.P.; Marks, I.N.; Mee, A.S.; Girdwood, A.D.; Bornman, P.C.; Gilinsky, N.H.; Tobias, R. and Lucke W.: Ranitidine in the treatment of gastric ulcer disease; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp.212–219 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  199. Yeo, T.; Delitala, G.; Bessen, G.M. and Edwards, C.R.W.: The effects of ranitidine on pituitary hormone secretion in vitro. British Journal of Clinical Pharmacology. Correspondence. 10: 171 (1980).Google Scholar
  200. Zeitoun, P.; d’Azemar, P.: International multicentre clinical trial of ranitidine in duodenal ulcer. Comparison with cimetidine; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine, Medicine Publishing Foundation Series 5, pp. 141–145 (Medicine Publishing Foundation, Oxford 1982).Google Scholar

Copyright information

© ADIS Press Australasia Pty Ltd (Inc. NSW) 1982

Authors and Affiliations

  • R. N. Brogden
    • 1
  • A. A. Carmine
    • 1
  • R. C. Heel
    • 1
  • T. M. Speight
    • 1
  • G. S. Avery
    • 1
  1. 1.ADIS Drug Information ServicesBirkenhead, Auckland 10New Zealand

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