Clinical Pharmacokinetics

, Volume 15, Issue 1, pp 44–56 | Cite as

Ranitidine Versus Cimetidine

A Comparison of Their Potential to Cause Clinically Important Drug Interactions
  • S. Rolf Smith
  • M. J. Kendall
Review Article Pharmacokinetic Drug Interactions

Summary

The literature on H2 - antagonist drug interactions is now extensive. The whole subject is so complicated as to make things difficult for the potential prescriber. However, it is possible to reduce most of the information contained in the literature to a few simple messages.

Firstly, H2 - antagonists bind to cytochrome P450 and may inhibit the metabolism of drugs eliminated by the mixed function oxygenase system. In this respect, cimetidine has a marked effect which, in most studies, has reached statistical significance. Ranitidine, on the other hand, has a much weaker effect which, even if demonstrable, is statistically non- significant. The potential benefit of rantidine, however, has to be weighed against the relative costs of the 2 drugs.

Secondly, H2 - antagonists inhibit gastric acid production and may alter the rate of gastric emptying, and hence the rate of drug absorption. They may also have some effect on portal vein and hepatic artery flow. However, these effects are small and probably not clinically relevant.

Thirdly, pharmacodynamic effects of H2 - antagonist-drug interactions are difficult to demonstrate in planned studies, and although they are reported from time to time, adverse reactions of consequence are relatively uncommon.

Fourthly, the prescriber needs to be aware that cimetidine may produce higher plasma concentrations of some drugs which have a fairly narrow therapeutic range, and this may be clinically important. Examples of drugs for which it may be undesirable to inadvertently increase plasma concentrations include warfarin, theophylline and phenytoin.

Finally, for most drugs metabolised by the liver, the risk of an important interaction is small. However, if such an interaction is noted it may be helpful to refer to the other reported cases, and a number of references are included here.

Keywords

Warfarin Theophylline Nifedipine Clinical Pharmacology Cimetidine 

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References

  1. Abernethy DR, Greenblatt DJ, Divoll M, Ameer B, Shader RI. Differential effect of cimietidine on drug oxidation (antipyrine and diazepam) vs. conjugation (acetaminophen and lorazepam): prevention of acetaminophen toxicity by cimetidine. Journal of Pharmacology and Experimental Therapeutics 224: 508–513, 1983PubMedGoogle Scholar
  2. Abernethy DR, Greenblatt DJ, Divoll M, Moschitto LJ, Harmatz JS, et al. Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam. Psychopharmacology 80: 275–278, 1983bPubMedCrossRefGoogle Scholar
  3. Abernethy DR, Greenblatt DJ, Shader RI. Imipramine-cimetidine interaction: impairment of clearance and enhanced absolute bioavailability. Journal of Pharmacology and Experimental Therapeutics 229: 702–705, 1984PubMedGoogle Scholar
  4. Algozzine GJ, Stewart RB, Sprenger PK. Decreased clearance of phenytoin with cimetidine. Annals of Internal Medicine 95: 244–245, 1981PubMedGoogle Scholar
  5. Al Kawas FH, Lenes BA, Sacher RA. Cimetidine and agranulocytosis. Annals of Internal Medicine 90: 922–923, 1979Google Scholar
  6. Anderson JR, Poklis A, Slavin RG. A fatal case of theophylline intoxication. Archives of Internal Medicine 143: 559–560, 1983PubMedCrossRefGoogle Scholar
  7. Bartle WR, Walker SE, Shapero T. Dose-dependent effect of cimetidine on phenytoin kinetics. Clinical Pharmacology and Therapeutics 33: 649–655, 1983PubMedCrossRefGoogle Scholar
  8. Bauer LA, Edwards AD, Randolph FD, Blouin RA. Cimetidine-induced decrease in lidocaine metabolism. American Heart Journal 198: 413–415, 1984CrossRefGoogle Scholar
  9. Bauman JH, Kimelblatt BJ, Caraccio TR, Silverman HM, Simon GI, et al. Cimetidine-theophylline interactions: report of four patients. Annals of Allergy 48: 100–103, 1982PubMedGoogle Scholar
  10. Bell JA, Gower A-J, Martin LE, Mills ENC, Smith WP. Interaction of H2 receptor antagonists with drug-metabolising enzymes. Biochemical Society Transactions 9: 113–114, 1981PubMedGoogle Scholar
  11. Benfield P, Clissold SP, Brogden RN. Metoprolol: an updated review of its pharmacodynamic properties and therapeutic efficacy. Drugs 31: 376–429, 1986PubMedCrossRefGoogle Scholar
  12. Benowitz NO, Meister W. Clinical pharmacokinetics of lidocaine. Clinical Pharmacokinetics 3: 177–201, 1978PubMedCrossRefGoogle Scholar
  13. Borg KO, Carlsson E, Hoffman KJ, Jonsson TW, Thorin H, et al. Metabolism of metoprolol (3H) in man, the dog and the rat. Acta Pharmacologica et Toxicologica 36 (Suppl. V): 125–135, 1975PubMedGoogle Scholar
  14. Breen KJ, Bury R, Desmond PV, Mashford ML, Morphett B, et al. Effects of cimetidine and rantidine on hepatic drug metabolism. Clinical Pharmacology and Therapeutics 31: 297–300, 1982PubMedCrossRefGoogle Scholar
  15. Burroughs AK, Walt RP, Dunk AA, Jenkins WJ, Sherlock S, et al. Effect of cimetidine on portal hypertension in cirrhotic patients. British Medical Journal 284: 1159–1160, 1982PubMedCrossRefGoogle Scholar
  16. Charbon GA, Bronwers HAA, Sala A. Histamine, H1 and H2 receptors in the gastrointestinal circulation. Naunyn-Schmiederberg’s Archives of Pharmacology 312: 123–129, 1980CrossRefGoogle Scholar
  17. Choonara IA, Cholerton S, Haynes BP, Breckenridge AM, Park BK. Stereoselective interaction between the R. enantiomer of warfarin and cimetidine. British Journal of Clinical Pharmacology 21: 271–277, 1986PubMedCrossRefGoogle Scholar
  18. Christian C, Meredith CG, Speeg KV. Cimetidine inhibits renal procainamide clearance. Clinical Pharmacology and Therapeutics 36: 221–227, 1984PubMedCrossRefGoogle Scholar
  19. Cluxton RJ, Rivera JO, Ritschel WA, Pesce AJ, Hanenson IB. Cimetidine-theophylline interaction. Annals of Internal Medicine 96: 684, 1982PubMedGoogle Scholar
  20. Cohen IA, Johnson CE, Berardi RR, Hyneck ML, Achem-karem SR. Effects of age and cimetidine dose on the magnitude of the cimetidine-theophylline drug interaction. Gastroenterology 86: 1050, 1984Google Scholar
  21. Curry SH, Devane CL, Wolfe MM. Cimetidine interaction with amitriptyline. European Journal of Clinical Pharmacology 29: 429–433, 1985PubMedCrossRefGoogle Scholar
  22. Dal Negro R, Pomari C, Zoccatelli O, Trevisan F, Carloni C, et al. Pharmacokinetics of theophylline and the H1 antagonist drugs cimetidine and ranitidine. International Journal of Clinical Pharmacology, Therapy and Toxicology 22: 221–226, 1984Google Scholar
  23. Dalton MJ, Powell JR, Messenheimer JA. The influence of cimetidine on single dose carbamazepine pharmacokinetics. Epilepsia 26: 127–130, 1985aPubMedCrossRefGoogle Scholar
  24. Dalton MJ, Powell JR, Messenheimer Jr JA. Ranitidine does not alter single-dose carbamazepine pharmacokinetics in healthy adults. Drug Intelligence and Clinical Pharmacy 19: 941–944, 1985bPubMedGoogle Scholar
  25. Daneshmend TK, Roberts CJC. Reduction in labetolol first pass metabolism following cimetidine. British Journal of Clinical Pharmacology 15: 153P, 1983Google Scholar
  26. Desmond PV, Mashford ML, Harman PJ, Morphett BJ, Breen KJ, et al. Decreased oral warfarin clearance after ranitidine and cimetidine. Clinical Pharmacology and Therapeutics 35: 338–341, 1984PubMedCrossRefGoogle Scholar
  27. Desmond PV, Patwardhan RV, Schenker S, Speeg KV. Cimetidine impairs elimination of chlordiazepoxide (librium) in man. Annals of Internal Medicine 93: 266–268, 1980PubMedGoogle Scholar
  28. Dobbs JH, Smith RN. Ranitidine and theophylline. Annals of Internal Medicine 100: 769, 1984PubMedGoogle Scholar
  29. Donn KH, Powell JR, Rogers JF, Eshelman FN. The influence of H2 receptor antagonists on steady-state concentrations of propranolol and 4-hydroxypropranolol. Journal of Clinical Pharmacology 24: 500–508, 1984aPubMedGoogle Scholar
  30. Donn KH, Powell JR, Rogers JF, Plachetka JR. Lack of effect of histamine H2 antagonists on indocyanine green disposition measured by two methods. Journal of Clinical Pharmacology 24: 360–370, 1984bPubMedGoogle Scholar
  31. Donovan MA, Heagerty AM, Patel L, Castleden M, Pohl JEF. Cimetidine and bioavailability of propranolol. Lancet 1: 164, 1981PubMedCrossRefGoogle Scholar
  32. Dunk AA, Jenkins WJ, Burroughs AK, Walt RP, Osuafor TOK, et al. 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: 117–120, 1983PubMedCrossRefGoogle Scholar
  33. Editorial. Lidocaine-cimetidine interaction can be toxic. Journal of the American Medical Association 247: 3174–3175, 1982Google Scholar
  34. Elliott P, Dundee JW, Elwood RJ, Collier PS. The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam. European Journal of Anaesthesiology 1: 245–251, 1984PubMedGoogle Scholar
  35. Feeley J, Guy E. Lack of effect of ranitidine on the disposition of lignocaine. British Journal of Clinical Pharmacology 15: 378–379, 1983CrossRefGoogle Scholar
  36. Feeley J, Wilkinson GR, McAllister CB, Wood AJJ. Increased toxicity and reduced clearance of lidocaine by cimetidine. Annals of Internal Medicine 96: 592–594, 1982Google Scholar
  37. Feeley J, Wilkinson GR, Wood AJJ. Reduction of liver blood flow and propranolol metabolism by cimetidine. New England Journal of Medicine 304: 692–695, 1981CrossRefGoogle Scholar
  38. Fenje PC, Isles AF, Baltodano A, MacLeod SM, Soldin S. Interaction of cimetidine and theophylline in two infants. Canadian Medical Association Journal 126: 1178, 1982PubMedGoogle Scholar
  39. Fernandes E, Melewicz FM. Ranitidine and theophylline. Annals of Internal Medicine 100: 459, 1984PubMedGoogle Scholar
  40. Friebel P, Walter-Sack I, Ukena D, Czechanowski B, De Vries J, et al. Influence of a single dose of cimetidine 800mg and ranitidine 300mg on oxidative drug transformation (antipyrine clearance). British Journal of Clinical Pharmacology 20: 546, 1985Google Scholar
  41. Frigo GM, Lecchini S, Carraraggi M, Gatti G, Tonini M, et al. Reduction in phenytoin clearance caused by cimetidine. European Journal of Clinical Pharmacology 25: 135–137, 1983PubMedCrossRefGoogle Scholar
  42. Gough PA, Curry SH, Araujo OE, Robinson JD, Dallman JJ. Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change. British Journal of Clinical Pharmacology 14: 739–742, 1982PubMedCrossRefGoogle Scholar
  43. Green AW, Ebling WF, Gardner MJ, Jusko WJ. Cimetidinemethylprednisolone-theophylline metabolic interaction. American Journal of Medicine 77: 1115–1118, 1984PubMedCrossRefGoogle Scholar
  44. Greenblatt DJ, Darrell MD, Abernethy R, Morse DS, Harmatz JS, et al. Clinical importance of the interaction of diazepam and cimetidine. New England Journal of Medicine 310: 1639, 1984PubMedCrossRefGoogle Scholar
  45. Greenblatt DJ, Locniskar A, Scavone JM, Blyden GT, Ochs HR, et al. Absence of interaction of cimetidine and ranitidine with intravenous and oral midazolam. Anaesthesia and Analgesia 65: 176–180, 1986Google Scholar
  46. Grigoleit HG, Hajdu P, Hundt HKL, Koeppen D, Malerczyk V, et al. Pharmacokinetic aspects of the interaction between clobazam and cimetidine. European Journal of Clinical Pharmacology 25: 139–142, 1983PubMedCrossRefGoogle Scholar
  47. Harvey CA, Owen DAA, Shaw KD. Evidence for both histamine H1 and H2 receptors in the gastric vasculature of the cat. British Journal of Pharmacology 69: 21–27, 1980PubMedCrossRefGoogle Scholar
  48. Heagerty AM, Donovan MA, Castleden CM, Pohl JF, Patel L, et al. Influence of cimetidine on pharmacokinetics of propranolol. British Medical Journal 282: 1917–1919, 1981PubMedCrossRefGoogle Scholar
  49. Henderson JM, Ibrahim SZ, Millikan WJ, Santi M, Warren WD. Cimetidine does not reduce liver blood flow in cirrhosis. Hepatology 3: 919–922, 1983PubMedCrossRefGoogle Scholar
  50. Henouer SA, Hollister LE. Cimetidine interaction with imipramine and nortriptyline. Clinical Pharmacology and Therapeutics 35: 183–187, 1984CrossRefGoogle Scholar
  51. Hetzel DJ, Bochner F, Hallpike JF, Shearman DJC. Cimetidine interaction with phenytoin. British Medical Journal 282: 1512, 1981PubMedCrossRefGoogle Scholar
  52. Houghton LA, Read NW. A comparative study of the effect of cimetidine and ranitidine on the rate of gastric emptying of liquid and solid test meals in man. Alimentary Pharmacology and Therapeutics 1: 401–408, 1987PubMedCrossRefGoogle Scholar
  53. Houghton GW, Richens A. Rate of elimination of tracer doses of phenytoin at different steady state serum phenytoin concentrations in epileptic patients. British Journal of Clinical Pharmacology 1: 155–161, 1974PubMedCrossRefGoogle Scholar
  54. Hsu K, Garton A, Sproule BJ, Tarn YK, Legatt D, et al. The influence of orally administered cimetidine and theophylline on the elimination of each drug in patients with chronic airways obstruction. American Review of Respiratory Disease 130: 740–743, 1984PubMedGoogle Scholar
  55. Jack DB, Quarterman CP, Zaman R, Kendall MJ. Variability of beta-blocker pharmacokinetics in young volunteers. European Journal of Clinical Pharmacology 23: 37–42, 1982PubMedCrossRefGoogle Scholar
  56. Kelly HW, Powell JR, Donohue JF. Ranitidine at very large doses does not inhibit theophylline elimination. Clinical Pharmacology and Therapeutics 39: 577–581, 1986PubMedCrossRefGoogle Scholar
  57. Kelly JG, Salem SAM, Kinney CD, Shanks RG, McDevitt DG. Effects of ranitidine on the disposition of metoprolol. British Journal of Clinical Pharmacology 19: 219–224, 1985PubMedCrossRefGoogle Scholar
  58. Kendall MJ, Laugher SJ, Wilkins MR. Ranitidine, cimetidine and metoprolol: a pharmacokinetic interaction study. Gastroenterology 90: 1940, 1986Google Scholar
  59. Kirch W, Hoensch H, Ohnhaus EE, Janisch HD. Ranitidine-nifedipine interaction. Deutsche Medizinische Wochenschrift 109: 1223, 1984PubMedGoogle Scholar
  60. Kirch W, Janisch HD, Heidemann H, Ramsch K, Ohnhaus EE. Effect of cimetidine and ranitidine on the pharmacokinetics and the antihypertensive action of nifedipine. Deutsche Medizinische Wochenschrift 108: 1757–1761, 1983bPubMedCrossRefGoogle Scholar
  61. Kirch W, Spahn H, Kohler H, Mutschler E. Accumulation and adverse effects of metoprolol and propranolol after concurrent administration of cimetidine. Archives of Toxicology 6: 379–383, 1983PubMedCrossRefGoogle Scholar
  62. Kirch W, Spahn H, Kohler H, Ohnhaus EE, Mutschler E. Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine. Klinische Wochenschrift 60: 1401–1407, 1982PubMedCrossRefGoogle Scholar
  63. Klotz U, Arvela P, Rosenkranz B. Effect of single doses of cimetidine and ranitidine on the steady state plasma levels of midazolam. Clinical Pharmacology and Therapeutics 38: 652–655, 1985PubMedCrossRefGoogle Scholar
  64. Klotz U, Reimann IW. Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam. European Journal of Pharmacology 18: 517–520, 1980aCrossRefGoogle Scholar
  65. Klotz U, Reimann I. Delayed clearance of diazepam due to cimetidine. New England Journal of Medicine 302: 1012–1014, 1980bPubMedCrossRefGoogle Scholar
  66. Klotz U, Reimann IW, Ohnhaus EE. Effect of ranitidine on the steady state pharmacokinetics of diazepam. European Journal of Clinical Pharmacology 24: 357–360, 1983PubMedCrossRefGoogle Scholar
  67. Knapp AB, Maguire W, Keren G, Karmen A, Levitt B, et al. Cimetidine-lidocaine interaction. Annals of Internal Medicine 98: 174–177, 1983PubMedGoogle Scholar
  68. Kornhauser DM, Wood AJJ, Vestal RE, Wilkinson GR, Branch RA, et al. Biological determinants of propranolol disposition in man. Journal of Clinical Pharmacology and Therapeutics 23: 165–174, 1978Google Scholar
  69. Lalonde RL, Koob RA, McLean WM, Balsys AJ. The effects of cimetidine on theophylline pharmacokinetics at steady state. Chest 83: 221–224, 1983PubMedCrossRefGoogle Scholar
  70. Lennard MS, Tucker GT, Woods HF. The polymorphic oxidation of β-adrenoceptor antagonists: clinical pharmacokinetic considerations. Clinical Pharmacokinetics 11: 1–17, 1986PubMedCrossRefGoogle Scholar
  71. Lobo J, Jack DB, Kendall MJ. The intra- and inter-subject variability of nifedipine pharmacokinetics in young volunteers. European Journal of Clinical Pharmacology 30: 57–60, 1986PubMedCrossRefGoogle Scholar
  72. Macphee GJA, Thompson GG, Scobie G, Agnew E, Park BK, et al. Effects of cimetidine on carbamazepine auto- and hetero-induction in man. British Journal of Clinical Pharmacology 18: 411–419, 1984PubMedCrossRefGoogle Scholar
  73. Mashford ML, Harman PJK, Morphett BS, Breen KJ, Desmond PV. Ranitidine does not affect chlormethiazole or indocyanine green disposition. Clinical Pharmacology and Therapeutics 34: 231–233, 1983PubMedCrossRefGoogle Scholar
  74. Mutschler E, Spahn H, Kirch W. The interaction between H2 receptor antagonists and β-adrenoceptor blockers. British Journal of Clinical Pharmacology 17: 51S–57S, 1984PubMedCrossRefGoogle Scholar
  75. Neuvonen PJ. Bioavailability of phenytoin. Clinical Pharmacokinetics 4: 91–103, 1979PubMedCrossRefGoogle Scholar
  76. Neuvonen PJ, Tokola RA, Kaste M. Cimetidine-phenytoin interaction. European Journal of Clinical Pharmacology 21: 215–220, 1981PubMedCrossRefGoogle Scholar
  77. Ochs HR, Greenblatt DJ, Gugler R, Muntefering G, Locniskar A, et al. Cimetidine impairs nitrazepam clearance. Clinical Pharmacology and Therapeutics 34: 227, 1983PubMedCrossRefGoogle Scholar
  78. Parker WA, MacLachlan RA. Prolonged hypnotic response to triazolam-cimetidine combination in an elderly patient. Drug Intelligence and Clinical Pharmacy 18: 980–981, 1984PubMedGoogle Scholar
  79. Patel L, Weerasuriya K. Effect of cimetidine and ranitidine on propranolol clearance. British Journal of Clinical Pharmacology 15: 152P, 1983Google Scholar
  80. Patwardhan RV, Johnson RF, Sinclair AP, Schenker S, Speeq KV. Lack of tolerance and rapid recovery of cimetidine-inhibited chlordiazepoxide (librium) elimination. Gastroenterology 81: 547–551, 1981PubMedGoogle Scholar
  81. Pawlik W, Tague LL, Tepperman BL, Miller TA, Jacobson ED. Histamine H1 and H2 receptor vasodilation of canine intestinal circulation. American Journal of Physiology 23: E219–224, 1977Google Scholar
  82. Powell JR, Foster J, Patterson H, Wargin W, Cross R. Single dose and steady state lidocaine disposition during oral and intravenous cimetidine administration. Clinical Pharmacology and Therapeutics 35: 267, 1984bGoogle Scholar
  83. Powell JR, Rogers JF, Wargin WA, Cross RE, Eshelman FN. Inhibition of theophylline clearance by cimetidine but not ranitidine. Archives of Internal Medicine 144: 484–486, 1984aPubMedCrossRefGoogle Scholar
  84. Quarterman CP, Kendall MJ, Jack DB. The effect of age on the pharmacokinetics of metoprolol and its metabolites. British Journal of Clinical Pharmacology 11: 287–294, 1981PubMedCrossRefGoogle Scholar
  85. Raemsch KD, Sommer J. Pharmacokinetics and metabolism of nifedipine. Hypertension 5 (Suppl.): 18–24, 1983Google Scholar
  86. Reimann IW, Klotz U, Frolich JC. Effects of cimetidine and ranitidine on steady-state propranolol kinetics and dynamics. Journal of Clinical Pharmacology and Therapeutics 32: 749–757, 1982CrossRefGoogle Scholar
  87. Reitberg DP, Bernhard H, Schentag J. Alteration of theophylline clearance and half-life by cimetidine in normal volunteers. Annals of Internal Medicine 95: 582–584, 1981PubMedGoogle Scholar
  88. Rendic S, Kajfez F, Ruf HH. Characterisation of cimetidine, ranitidine and related structures interaction with cytochrome P450. Drug Metabolism and Disposition 11: 137–142, 1983PubMedGoogle Scholar
  89. Roberts RK, Grice J, Wood L, Petraff V, McGuffie C. Cimetidine impairs the elimination of theophylline and antipyrine. Gastroenterology 81: 19–21, 1981PubMedGoogle Scholar
  90. Robson RA, Wing LMH, Miners JO, Lillywhite KJ, Birkett DJ. The effect of ranitidine on the disposition of lignocaine. British Journal of Clinical Pharmacology 20: 170–173, 1985PubMedCrossRefGoogle Scholar
  91. Salem RB, Breland BD, Mishra SK, Jordan JE. Effect of cimetidine on phenytoin serum levels. Epilepsia 24: 284–288, 1983PubMedCrossRefGoogle Scholar
  92. Sazie E, Jaffe JP. Severe granulocytopenia with cimetidine and phenytoin. Annals of Internal Medicine 93: 151–152, 1980PubMedGoogle Scholar
  93. Serlin MJ, Sibeon RG, Breckenridge AM. Lack of effect of ranitidine on warfarin action. British Journal of Clinical Pharmacology 12: 791–794, 1981PubMedCrossRefGoogle Scholar
  94. Serlin MJ, Sibeon RG, Mossman S, Breckenridge AM. Cimetidine: interaction with oral anticoagulants in man. Lancet 2: 317–319, 1979PubMedCrossRefGoogle Scholar
  95. Shapiro PA. Cimetidine-imipramine interaction: case report and comments. American Journal of Psychiatry 141: 152–153, 1984Google Scholar
  96. Silver BA, Bell WR. Cimetidine potentiation of the hypoprothrombinemic effects of warfarin. Annals of Internal Medicine 90: 348–349, 1979PubMedGoogle Scholar
  97. Smith MJ, Benyunes MC, Bjornsson TD, Shand DG, Pritchett ELC. Influence of cimetidine on verapamil kinetics and dynamics. Clinical Pharmacology and Therapeutics 36: 551–554, 1984PubMedCrossRefGoogle Scholar
  98. Smith SR, Kendall MJ, Lobo J, Beerahee A, Jack DB, et al. Ranitidine and cimetidine: drug interactions with single dose and steady-state nifedipine administration. British Journal of Clinical Pharmacology 23: 311–315, 1987PubMedCrossRefGoogle Scholar
  99. Somogyi A, 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, 1984PubMedCrossRefGoogle Scholar
  100. Somogyi A, Gugler R. Drug interactions with cimetidine. Clinical Pharmacokinetics 7: 23–41, 1982PubMedCrossRefGoogle Scholar
  101. Somogyi A, McLean A, Heinzow B. Cimetidine-procainamide pharmacokinetic interaction in man: evidence of competition for tubular secretion of basic drugs. European Journal of Clinical Pharmacology 25: 339–345, 1983PubMedCrossRefGoogle Scholar
  102. Sorkin EM, Clissold SP, Brogden RN. Nifedipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs 30: 182–253, 1985PubMedCrossRefGoogle Scholar
  103. Spahn H, Mutschler E, Kirch W, Hoensch H, Ohnhaus EE. Influence of ranitidine on plasma metoprolol concentrations. British Medical Journal 287: 838, 1983PubMedCrossRefGoogle Scholar
  104. Spahn H, Mutschler E, Kirch W, Ohnhaus EE, Janisch HD. Influence of ranitidine on plasma metoprolol and atenolol concentrations. British Medical Journal 286: 1546–1547, 1983PubMedCrossRefGoogle Scholar
  105. Speeg Jr KV, Patwardhan RV, Avant GR, Mitchell MC, Schenker S. Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents. Gastroenterology 82: 89–96, 1982PubMedGoogle Scholar
  106. Terry RW. Nifedipine therapy in angina pectoris: evaluation of safety and side effects. American Heart Journal 104: 681, 1982PubMedCrossRefGoogle Scholar
  107. Toon S, Hopkins KJ, Garstang FM, Rowland M. Comparative effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of warfarin in man. European Journal of Clinical Pharmacology 32: 165–172, 1987PubMedCrossRefGoogle Scholar
  108. Tyden G, Thulin L, Nyberg B. The effect of cimetidine on liver blood flow in anaesthetized man. Acta Chirurgica Scandinavica 149: 303–305, 1983PubMedGoogle Scholar
  109. Vestal RC, Thummel KE, Musser B. Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration. British Journal of Clinical Pharmacology 15: 411–418, 1983PubMedCrossRefGoogle Scholar
  110. Watts RW, Hetzel DJ, Bochner F, Hallpike JF, Hanns CS, et al. Lack of interaction between ranitidine and phenytoin. British Journal of Clinical Pharmacology 15: 499–500, 1983PubMedCrossRefGoogle Scholar
  111. Webster LK, Mihaly GW, Jones DB, Smallwood RA, Phillips JA, et al. Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics. European Journal of Clinical Pharmacology 27: 341–343, 1984PubMedCrossRefGoogle Scholar
  112. Weinberger MM, Smith G, Milavetz G, Hendeles L. Decreased theophylline clearance due to cimetidine. New England Journal of Medicine 304: 672, 1981PubMedGoogle Scholar
  113. Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390, 1975PubMedGoogle Scholar
  114. Wing LMH, Miners JO, Birkett DJ, Foenander T, Lillywhite K, et al. Lidocaine disposition: sex differences and effects of cimetidine. Clinical Pharmacology and Therapeutics 35: 695–701, 1984PubMedCrossRefGoogle Scholar
  115. Winship LC, McKenney JM, Wright JT, Wood JH, Goodman RP. The effect of ranitidine and cimetidine on single dose diltiazem pharmacokinetics. Pharmacotherapy 5: 16–19, 1985PubMedGoogle Scholar
  116. Woods KL, Linton SP, Kendall MJ, Faragher EB, Grieve RJ. Exercise response of healthy subjects in the evaluation of cardioselectivity of beta blockers. European Journal of Clinical Pharmacology 15: 229–233, 1979PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press Limited 1988

Authors and Affiliations

  • S. Rolf Smith
    • 1
  • M. J. Kendall
    • 1
  1. 1.Department of Pharmacology, The Medical SchoolUniversity of BirminghamEdgbaston, BirminghamEngland

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