Clinical Pharmacokinetics

, Volume 9, Issue 6, pp 493–510

Interactions and Non-interactions with Ranitidine

  • W. Kirch
  • H. Hoensch
  • H. D. Janisch
Review Articles

Summary

At present, there are two H2-receptor antagonists available for the treatment of peptic ulcer disease — cimetidine and ranitidine. Cimetidine is well known to interact with a number of concurrently administered drugs. Like cimetidine, ranitidine binds to cytochrome P-450 in the liver where it appears to exert an inhibitory effect, but to a lesser extent than cimetidine. Both H2-receptor antagonists may also reduce hepatic blood flow.

Several drugs which are known to interact with cimetidine have been found not to interact significantly with ranitidine, including propranolol, lignocaine, phenytoin and diazepam. However, significant pharmacokinetic interactions between ranitidine and several other drugs have been established. These interactions may be attributed variously to an effect of ranitidine on hepatic metabolism or to an effect on the absorption of concomitantly administered drugs. For example, the bioavailability of midazolam is significantly increased due to the influence of ranitidine on gastric pH and thus on absorption of midazolam, leading to an increased soporific effect of this benzodiazepine; an effect of ranitidine on oxidative liver metabolism also appears to be a contributory factor in this interaction. Conversely, ranitidine distinctly reduced protein-bound cobalamin absorption from a mean of 7.66% prior to ranitidine administration to 0.84% during treatment with ranitidine 300mg daily.

A significant pharmacokinetic interaction has also been demonstrated between ranitidine and procainamide: the AUC of procainamide increased and the renal clearance fell significantly from a mean of 378 to 309 ml/min with ranitidine co-administration. However, this interaction is due to a different mechanism. In this case, ranitidine appears to compete with procainamide for the common renal proximal tubular secretion site.

The reported interactions of ranitidine with warfarin, metoprolol, nifedipine, theophylline and fentanyl appear to be due to inhibition of cytochrome P-450. In a clinical study, warfarin clearance was significantly reduced from 66.7 to 48.7 ml/min by ranitidine, and by cimetidine to 42.9 ml/min. Similarly, the elimination half-lives of metoprolol and nifedipine were distinctly prolonged and the AUCs significantly increased by ranitidine. However, the latter pharmacokinetic interactions appear unlikely to be of clinical significance since the clinical effects of metoprolol and nifedipine were unaffected by ranitidine treatment. In therapeutic concentrations, ranitidine inhibited the disappearance of fentanyl from an in vitro microsomal preparation, indicating that it inhibits microsomal drug metabolism. In rat experiments, ranitidine also significantly reduced alcohol elimination by 19% (p < 0.01).

The bioavailability of ranitidine itself was decreased by 33% due to concurrent administration of an aluminium-magnesium hydroxide antacid preparation (p < 0.05), and increased by propantheline (p < 0.05). The anticholinergic drug pirenzepine also produced a pharmacodynamic interaction with ranitidine, potentiating the inhibitory effect of the latter on gastric acid secretion.

Thus present data show that ranitidine is involved in drug interactions which may be of clinical relevance. Adverse drug interactions can be avoided by careful monitoring of treated patients and adjustment of the dosage where appropriate.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abernethy, D.R.; Greenblat, D.J.; Eshelman, F.N. and Shader, R.I.: Ranitidine does not impair oxidative or conjugative metabolism: Noninteraction with antipyrine, diazepam, and lorazepam. Clinical Pharmacology and Therapeutics 35: 188 (1984).PubMedCrossRefGoogle Scholar
  2. Arditi, M.; Cravetto, C.; Molino, G.; Pera, A. and Penti, V.: The effect of chronic treatment with gastric antisecretory drugs on functional liver plasma flow. Gastroenterology 84: 1092 (1983).Google Scholar
  3. Barber, H.E.; Petrie, J.C. and Smith, K.J.: A comparison of cimetidine and ranitidine: Effect on liver blood flow. Proceedings of the Pharmacological Society, London, January 4–6 (1984).Google Scholar
  4. Breen, K.J.; Bury, R.; Desmond, P.V.; Mostfond, M.L.; Morphelt, B.; Westwood, B. and Shaw, R.G.: Effects of cimetidine and ranitidine on hepatic drug metabolism. Clinical Pharmacology and Therapeutics 31: 297 (1982).PubMedCrossRefGoogle Scholar
  5. Brogden, R.N.; Carmine, A.A.; Heel, R.C.; Speight, T.M. and Avery G.S.: Ranitidine: A review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases. Drugs 24: 267 (1982).PubMedCrossRefGoogle Scholar
  6. Brown, H.C.; Carruthers, S.G.; Johnston, G.B.; Kelly, J.G.; McAinsh, J.; McDevitt, D.G. and Shanks, R.G.: Clinical pharmacologic observations on atenolol, a ′8-adrenoceptor blocker. Clinical Pharmacology and Therapeutics 20: 524 (1976).PubMedGoogle Scholar
  7. Burroughs, A.K.; Walt, R.P.; Dunk, A.A.; Jenkins, W.J.; Sherlock, S.; Mackie, S. and Dick, R.: Effect of cimetidine on portal hypertension in cirrhotic patients. British Medical Journal 284: 1159 (1982).PubMedCrossRefGoogle Scholar
  8. 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: 161–168 (1981).PubMedCrossRefGoogle Scholar
  9. Chau, N.P.; Zech, P.Y.; Pozet, N. and Hadj-Aissa, A.: Ranitidine kinetics in normal subjects. Clinical Pharmacology and Therapeutics 31: 770 (1982).PubMedCrossRefGoogle Scholar
  10. Dammann, G.H.; Müller, P. and Simon, B.: 24-Hour intragastric acidity and single night-time doses of three H2-blockers. Lancet 2: 1078 (1983).PubMedCrossRefGoogle Scholar
  11. Desmond, P.V.; Mashford, M.L.; Harman, P.J.; Morphett, B.J.; Breen, K.J. and Wang, Y.M.: Decreased oral warfarin clearance after ranitidine and cimetidine. Clinical Pharmacology and Therapeutics 35: 338 (1984).PubMedCrossRefGoogle Scholar
  12. Desmond, P.V.; Shaw, G.; Bury, R.W. and Breen, K.J.: No effect of ranitidine on the disposition or elimination of chlormethiazole or indocyanide green. Scandinavian Journal of Gastroenterology 17: 50 (1982).Google Scholar
  13. Dobbs, J.H.; Skoutakis, V.A.; Acchiander, S.R. and Dobbs, B.R.: Effect of aluminium hydroxide on the absorption of propranolol. Current Therapeutic Research 21: 887 (1977).Google Scholar
  14. Dunk, L.A.; Jenkins, W.J.; Burroughs, A.K.; Watt, R.P.; Osuafar, T.O.K.; Sherlock, S.; Mackie, A. and Dick, R.: The effect of ranitidine on the plasma clearance and hepatic extraction of indocyanine green in patients with chronic liver disease. British Journal of Clinical Pharmacology 16: 117 (1983).PubMedCrossRefGoogle Scholar
  15. Elliot, P.; Dundee, J.W.; Elwood, R.J.; Collier, P.S. and McClean, E.: The influence of two H2-receptor antagonists on the systemic availability of two benzodiazepines, midazolam and temazepam. Proceedings of the British Pharmacological Society, London, January 4-6 (1984).Google Scholar
  16. Elwood, R.J.; Hildebrand, P.J.; Dundee, J.W. and Collier, P.S.: Ranitidine influences uptake of oral midazolam. British Journal of Clinical Pharmacology 15: 743 (1983).PubMedCrossRefGoogle Scholar
  17. Eshelman, F.N.; Plachetka, J.R. and Brown, B.C.P.: Effect of antacid and anticholinergic medication on ranitidine absorption. Clinical Pharmacology and Therapeutics 33: 216 (1983).Google Scholar
  18. Feely, J. and Guy, E.: Ranitidine also reduces liver blood flow. Lancet 1: 169 (1982).CrossRefGoogle Scholar
  19. Feely, J. and Guy, E.: Lack of effect of ranitidine on the disposition of lidocaine. British Journal of Clinical Pharmacology 15: 378 (1983).PubMedCrossRefGoogle Scholar
  20. Feely, J.; Wilkinson, G.R. and Wood, A.R.: Reduction of liver blood flow and propanolol metabolism by cimetidine. New England Journal of Medicine 304: 692 (1981).PubMedCrossRefGoogle Scholar
  21. Fernandez, E. and Melewicz, F.M.: Ranitidine and theophylline. Annals of Internal Medicine 100: 459 (1984).Google Scholar
  22. Garg, D.C.; Weidler, D.J.; Jallad, S. and Eshelman, F.N.: The effects of ranitidine and cimetidine on hepatic blood flow. Clinical Pharmacology and Therapeutics 31: 228 (1982).Google Scholar
  23. Garg, D.C.; Weidler, D.J. and Eshelmann, F.N.: Ranitidine bio-availability and kinetics in normal male subjects. Clinical Pharmacology and Therapeutics 33: 445 (1983).PubMedCrossRefGoogle Scholar
  24. Gledhill, T.; Howard, D.M.; Buck, M.; Paul, A. and Hunt, R.H.: Single nocturnal dose of an H2-receptor antagonist for the treatment of duodenal ulcer. Gut 24: 904 (1983).PubMedCrossRefGoogle Scholar
  25. Gugler, R.; Brand, M. and Somogyi, A.: Impaired cimetidine absorption by antacids and metoclopramide. European Journal of Clinical Pharmacology 20: 225 (1981).PubMedCrossRefGoogle Scholar
  26. Hansen, W.E. and Bertl, S.: Hemmung der Azetylcholinesterasen — ein relevanter Nebeneffekl von Ranitidin?. Zeitschrift für Gastroenlerologie 21: 164 (1983).Google Scholar
  27. Heagerty, A.M.; Castleden, C.M. and Patel, L.: Failure of ranitidine to interact with propranolol. British Medical Journal 284: 1304 (1982).PubMedCrossRefGoogle Scholar
  28. Heagerty, A.M.; Donovan, M.A.; Castleden, C.M.; Pohl, J.I.; Patel, L. and Hedges, A.: Influence of cimetidine on pharmacokinetics of propranolol. British Medical Journal 282: 1917 (1981).PubMedCrossRefGoogle Scholar
  29. Hecken van, A.M.; Tjandramaga, T.B.; Mullie, A.; Verbesselt, R. and De Schepper, F.J.: Ranitidine single dose pharmacokinetics and absolute bioavailablity in man. British Journal of Clinical Pharmacology 14: 195 (1982).PubMedCrossRefGoogle Scholar
  30. Henry, B.A.; MacDonald, I.A.; Kitelington, G.; Bill, G.D. and Longman, M.J.S.: Cimetidine and ranitidine comparison of effects on hepatic drug metabolism. British Medical Journal 281: 775 (1980).PubMedCrossRefGoogle Scholar
  31. Hoensch, H.; Hartmann, F.; Schomerus, H.; Bieck, P. and Dölle, W.: Monooxygenase enzyme activity in alcoholics with varying degrees of liver disease. Gut 20: 666 (1979).PubMedCrossRefGoogle Scholar
  32. Hoensch, H.; Hutzel, H.; Kirch, W. and Ohnhaus, E.E.: Isolation of human hepatic microsomes and their inhibition by cimetidine and ranitidine. European Journal of Clinical Pharmacology (In press, 1984).Google Scholar
  33. Jackson, J.E.; Bentley, J.B.; Glass, S.; Banner, W. and Plachetka, J.B.: The effects of H2 blockers on lidocaine disposition. (Abstract.) Clinical Pharmacology and Therapeutics 33: 255 (1983).Google Scholar
  34. Kanto, J.; Allonen, H.; Jalonen, H. and Härtyle, R.: The effect of metoclopramide and propanethline on the gastro-intestinal absorption of cimetidine. British Journal of Clinical Pharmacology 11: 527 (1981).CrossRefGoogle Scholar
  35. Kelly, J.G.; Shanks, R.G. and McDevitt, D.G.: Influence of ranitidine on plasma metoprolol concentrations. British Medical Journal 287: 1218 (1983).CrossRefGoogle Scholar
  36. Kirch, W.; Hoensch, H.; Ohnhaus, E.E. and Janisch, H.D.: Ranitidin-Nifedipin Interaktion. Deutsche Medizinische Wochenschrift 109: 1223 (1984).PubMedGoogle Scholar
  37. Kirch, W.; Janisch, H.D.; Heidemann, H.; Rämsch, K. and Ohnhaus, E.E.: Der Einfluβ von Cimetidin und Ranitidin auf Pharmakokinctik und antihypertensiven Effekt von Nifedipin. Deutsche Medizinische Wochenschrift 108: 1757 (1983a).PubMedCrossRefGoogle Scholar
  38. Kirch, W.; Köhler, H.; Mutschler, E. and Schäfer, M.: Pharmacokinetics of atenolol in relation to renal function. European Journal of Clinical Pharmacology 19: 65 (1981c).PubMedCrossRefGoogle Scholar
  39. Kirch, W.; Köhler, H.; Spahn, H. and Mutschler, E.: Interaction of cimetidine with metoprolol, propranolol or atenolol. Lancet 2: 331 (1981a).Google Scholar
  40. Kirch, W.; Schäfer-Korting, M.; Mutschler, E.; Ohnhaus, E.E. and Brown, W.: Clinical experience with atenolol in patients with chronic liver disease. Journal of Clinical Pharmacology 23: 171 (1983b).PubMedGoogle Scholar
  41. Kirch, W.; Schäfer-Korting, H.; Axthelm, T.; Köhler, H. and Mutschler, E.: Interaction of atenolol with concurrent administration of furosemide, calcium or aluminium hydroxide. Clinical Pharmacology and Therapeutics 30: 429 (1981b).PubMedCrossRefGoogle Scholar
  42. Klotz, U.; Reimann, I.W. and Ohnhaus, E.E.: Effect of ranitidine on steady state pharmacokinetics of diazepam. European Journal of Clinical Pharmacology 24: 357 (1983).PubMedCrossRefGoogle Scholar
  43. Klotz, U. and Reimann, J.: Influence of cimetidine on pharmacokinetics of desmethyldiazepam and oxazepam. European Journal of Clinical Pharmacology 18: 517 (1980).PubMedCrossRefGoogle Scholar
  44. Koch-Weser, J. and Klein, S.W.: Procainamide dosage schedules, plasma concentrations and clinical effects. Journal of the American Medical Association 215: 1454 (1971).PubMedCrossRefGoogle Scholar
  45. Lebert, P.A.; Macleod, S.M.; Mahon, W.A.; Soldin, S.J.; Fenge, P. and Vandenberghe, H.M.: Ranitidine kinetics and dynamics: I. Oral dose studies. Clinical Pharmacology and Therapeutics 30: 439 (1981a).CrossRefGoogle Scholar
  46. 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: 457 (1981b).Google Scholar
  47. Lebrec, D.; Goldfarb, G. and Benhamou, J.P.: Reduction of liver blood flow by cimetidine. New England Journal of Medicine 305: 100 (1981).CrossRefGoogle Scholar
  48. Lecoque, F.R. and McPhaul, J.J.: The effects of starvation, high fat diets and before infusions on uric acid balance. Metabolism 14: 186 (1965).CrossRefGoogle Scholar
  49. Lee, M.R.; Gandolfi, A.J.; Sipes, I.G. and Bentley, J.: Effect of histamine H2-receptors on fentanyl metabolism. Pharmacologist 24: 282 (1982).Google Scholar
  50. Leevy, C.M.; Leevy, C.B. and Howard, N.M.: Indocyanine green and the liver; in Davidson (Ed). Problems in Liver Disease, p. 42 (Stratton, New York 1979).Google Scholar
  51. Lelaiche, J.; Catton, D.; Zittonn, J.; Marguet, J. and Yvart, J.: Effect of ranitidine on cobalamin absorption. Digestive Diseases and Science 28: 667 (1983).Google Scholar
  52. Lennard, M.S.; Silas, J.H.; Freestone, S.; Ramsey, L.E.; Tucker, G.T. and Woods, H.F.: Oxidative phenotype — a major determinant of metoprolol metabolism and response. New England Journal of Medicine 307: 1558 (1982).PubMedCrossRefGoogle Scholar
  53. Londong, W.; Londong, V.; Ebert, H.; Pöch, G.; Bozler and Gugler, R.: Interaktion von Ranitidin und Pirenzipin. Zeitschrift fur Gastroenterologie 384: 384 (1983).Google Scholar
  54. Louis, W.J.; Mihaly, G.W.; Hanson, R.G.; Anderson, A.; McNeil, J.J.; Yeomans, N.D. and Smallwood, R.A.: Pharmacokinetic and gastric secretory studies of ranitidine in man. Scandinavian Journal of Gastroenterology 16 (Suppl. 69): 11 (1981).Google Scholar
  55. 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
  56. Mashford, M.L.; Harman, P.J.; Morphett, B.J.; Breen, K.J. and Desmond, P.V.: Ranitidine does not affect chlormethiazole or indocyanine green disposition. Clinical Pharmacology and Therapeutics 34: 231 (1983).PubMedCrossRefGoogle Scholar
  57. Mayersohn, M.: Physiological factors that modify systemic drug availability and pharmacologic response in clinical practice in Blanchard et al. (Eds.) Principles and Perspectives in Drug Bioavailability, p. 211 (Karger, Basel 1979).Google Scholar
  58. McGowan, W.A.W. and Dundee, J.W.: The effect of intravenous cimetidine on the absorption of orally administered diazepam and lorazepam. British Journal of Clinical Pharmacology 14: 207 (1982).PubMedCrossRefGoogle Scholar
  59. McCarthy, B.M.: Ranitidine or cimetidine. Annals of Internal Medicine 99: 551 (1983).PubMedGoogle Scholar
  60. McFadyen, M.L.; Folb, P.I.; Miller, R.; Marks, I.N. and Moshal, M.G.: The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration: A comparison of responders and non-responders. European Journal of Clinical Pharmacology 24: 441 (1983).PubMedCrossRefGoogle Scholar
  61. 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, p. 41 (Medicine Publishing Foundation, Oxford1982).Google Scholar
  62. Mignon, M.; Chau, N.P.; Nguyen-Phuoc, B.K.; Sauvage, B.; Leguy, F. and Bonfils, S.: Ranitidine upon meal-induced gastric secretion: Oral pharmacokinetics and plasma concentration effect relationships. British Journal of Clinical Pharmacology 14: 187 (1982).PubMedCrossRefGoogle Scholar
  63. Mihaly, G.W.; Marino, A.T.; Webster, L.K. and Jones, D.B.: High doses of antacid (Mylama II) reduces bioavailability of ranitidine. British Medical Journal 285: 998 (1982).PubMedCrossRefGoogle Scholar
  64. Mitchell, M.C.; Schenker, S. and Speeg, K.V.: Differential effects of cimetidine and other H2-receptor antagonists on acetaminophen metabolism. Clinical Research 79: 758 (1981).Google Scholar
  65. Ohnhaus, E.E.: The effect of different administration periods on the time course of enzyme induction in man. Clinical Pharmacology and Therapeutics 33: 259 (1983).Google Scholar
  66. Patel, L. and Weerasuriya, K.: Effect of cimetidine and ranitidine on propranolol clearance. British Journal of Clinical Pharmacology 15: 152 (1983).Google Scholar
  67. Powell, J.R.; Rogers, J.F.; Wargin, W.A.; Cross, R.E. and Eshelman, F.N.: Influence of cimetidine versus ranitidine on theophylline pharmacokinetics. Clinical Pharmacology and Therapeutics 31: 261 (1982).Google Scholar
  68. Puurunen, J.; Sotaniemi, E. and Pelkonen, O.: Effect of cimetidine on microsomal drug metabolism in man. European Journal of Clinical Pharmacology 18: 185 (1980).PubMedCrossRefGoogle Scholar
  69. Reeves, P.R.; McAinsh, J.; McIntosh, D.A.D. and Winrow, M.J.: Metabolism of atenolol in man. Xenobiotica 8: 313 (1978).PubMedCrossRefGoogle Scholar
  70. Reimann, W.; Klotz, U. and Fröhlich, J.C.: Effects of cimetidine on steady state propranolol kinetics. Clinical Pharmacology and Therapeutics 32: 749 (1982).PubMedCrossRefGoogle Scholar
  71. Rendić, S.; Alebic-Kolbah, T. and Kajfez, F.: Interaction of ranitidine with liver microsomes. Xenobiotica 12: 9 (1982).PubMedCrossRefGoogle Scholar
  72. Rendić, S.; Kajfez, F. and Ruf, H.H.: Characterization of cimetidine, ranitidine and related structures. Interaction with cytochrome P 450. Drug Metabolism and Disposition 11: 137 (1983).PubMedGoogle Scholar
  73. Roberts, A.P.; Harrison, C.; Dixon, G.T. and Curtis, J.R.: Plasma ranitidine concentrations after intravenous administration in normal volunteers and haemodialysis patients. Postgraduate Medical Journal 59: 25 (1983).PubMedCrossRefGoogle Scholar
  74. Roberts, C.J.C.: Clinical pharmacokinetics of ranitidine. Clinical Pharmacokinetics 9: 211 (1984).PubMedCrossRefGoogle Scholar
  75. Rowland, M.; Benet, L.Z. and Graham, G.G.: Clearance concepts in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 1: 123 (1973).PubMedCrossRefGoogle Scholar
  76. Schiller, K.F.R.: Short term treatment of duodenal ulcer. Comparisons of ranitidine with cimetidine: UK data; in Misiewicz and Wormsley (Eds) The Clinical Use of Ranitidine Medicine Publishing Foundation Series 5, p. 157 (Medicine Publishing Foundation, Oxford 1982).Google Scholar
  77. Seitz, H.K.; Bösche, J.; Cruppa, P.; Simon, B. and Veith, S.: Effekt der H2-Rezeptoren Antagonisten Cimetidin und Ranitidin auf die in-vivo Äthanolelimination bei der Ratte. Zeitschrift für Gastroenterologie 20: 493 (1982).Google Scholar
  78. Seitz, H.K.; Bösch, J.; Czyan, P.; Veith, S.; Simon, B. and Kaonmerell, B.: Increased blood alcohol levels following cimetidine but not ranitidine. Lancet 1: 760 (1983).PubMedCrossRefGoogle Scholar
  79. 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).PubMedCrossRefGoogle Scholar
  80. Serlin, M.J.; Sibeon, R.G.; Mossmann, S.; Breckenridge, A.M.; Williams, J.R.B.; Atwood, J.L. and Willoughby, J.M.T.: Cimetidine: Interaction with oral anticoagulants in man. Lancet 2: 317 (1979).PubMedCrossRefGoogle Scholar
  81. Seqing, 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
  82. Somogyi, A. and Gugler, R.: Drug interaction with cimetidine. Clinical Pharmacokinetics 7: 23 (1982).PubMedCrossRefGoogle Scholar
  83. Somogyi, A. and Heinzow, B.: Cimetidine reduces procainamide elimination. New England Journal of Medicine 304: 1080 (1982).Google Scholar
  84. Somogyi, A. and Bochner, F.: Dose and concentration dependent effect of ranitidine on procainamide disposition and renal clearance in man. British Journal of Clinical Pharmacology 18: 175–181 (1984).PubMedCrossRefGoogle Scholar
  85. Spahn, H.; Kirch, W. and Mutschler, E.: The interaction of cimetidine with metoprolol, atenolol, propranolol, pindolol and penbutolol. British Journal of Clinical Pharmacology 15: 500 (1983a).PubMedCrossRefGoogle Scholar
  86. Spahn, H.; Mutschler, E.; Kirch, W.; Ohnhaus, E.E. and Janisch, H.D.: Influence of ranitidine on plasma metoprolol and atenolol concentrations. British Medical Journal 286: 1546 (1983b).PubMedCrossRefGoogle Scholar
  87. Speeg, K.V.; Rattmandhan, R.V.; Amant, G.R.; Mitchell, M.C. and Schenker, S.C.: Inhibition of microsomal drug metabolism by histamine-H2-receptor antagonists studied in vivo and in vitro in rodents. Gastroenterology 82: 89 (1982).PubMedGoogle Scholar
  88. Staiger, C.; Simon de Vries, B.; Katter, H. and Walter, E.: Untersuchungen zur Wirkung von Ranitidine auf den Antipyrin-Metabolismus. Zeitschrift für Gastroenterologie 18: 601 (1980).PubMedGoogle Scholar
  89. Streeter, A.M.; Goulston, K.J.; Bathur, F.A.; Hilmer, R.S.; Crone, G.G. and Pheils, M.T.: Cimetidine and malabsorption of cobalamin. Digestive Diseases and Science 27: 13 (1982).CrossRefGoogle Scholar
  90. Tarditi, E.; Valenti, G.; Scarpignato, C. and Bentaccini, G.: Impared TSH response to TRH after intravenous ranitidine in man. Experientia 39: 109 (1983).PubMedCrossRefGoogle Scholar
  91. Walt, R.P.; Male, 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 (1981).PubMedCrossRefGoogle Scholar
  92. Watts, R.W.; Hetzel, D.J.; Bochner, F.; Hallpike, J.F.; Hann, C.S. and Sherman, B.J.: Lack of interaction between ranitidine and phenytoin. British Journal of Clinical Pharmacology 15: 499 (1983).PubMedCrossRefGoogle Scholar
  93. Wilkinson, G.R. and Shand, D.G.: A physiological approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 337 (1975).Google Scholar
  94. Young, C.J.; Daneshmend, T.K. and Roberts, C.J.: Effects of cirrhotic and ageing on the elimination and bioavailability of ranitidine. Gut 23: 819 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press Limited 1984

Authors and Affiliations

  • W. Kirch
    • 1
    • 2
  • H. Hoensch
    • 1
    • 2
  • H. D. Janisch
    • 1
    • 2
  1. 1.Medical DepartmentUniversity of Essen School of MedicineEssenGermany
  2. 2.Department of GastroenterologyKlinikum CharlottenburgBerlinGermany
  3. 3.Oberarzt, Medizinische Klinik und PoliklinikUniversitätsklinikumEssen 1Federal Republic of Germany

Personalised recommendations