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Pharmacokinetic and Pharmacodynamic Properties of Histamine H2-Receptor Antagonists

Relationship Between Intrinsic Potency and Effective Plasma Concentrations

  • Review Article
  • Pharmacokinetic-Pharmacodynamic Relationships
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Summary

Histamine H2-receptor antagonists are a unique class of compounds. Pharmacologically they are characterised as a family by their ability to inhibit the secretion of gastric acid, and kinetically they are classified as a family by their similarity in absorption, distribution and elimination.

All the H2-receptor antagonists exhibit classical competitive drug-receptor interactions, with Schild slope parameters not significantly different from unity. Comparison of the values of the negative logarithm of the molar concentration of antagonist in the presence of which the potency of the agonist is reduced 2-fold (PA2) indicates that famotidine is about 20 to 50 times more potent than cimetidine and 6 to 10 times more potent than ranitidine. To date, famotidine is the most potent among marketed H2-receptor antagonists.

Oral absorption of all the H2-receptor antagonists under clinical investigation is fairly rapid. Peak plasma concentrations are usually attained within 1 to 3h after the dose, but a second peak after oral administration has been observed with cimetidine, ranitidine, famotidine, ramixotidine and etintidine. The mean oral bioavailability for the H2-antagonists ranges from 50 to 70%.

Reports on the plasma profiles after intravenous administration are available only for cimetidine, ranitidine, famotidine and nizatidine: plasma concentrations of all 4 decline in a biexponential manner. All of the H2-antagonists are eliminated quite rapidly, with a terminal half-life of 1 to 3h and a total body clearance of 24 to 48 L/h. Elimination is mainly attributable to renal excretion, with renal clearances ranging from 13.8 to 30 L/h. As the values for renal clearance greatly exceed the glomerular filtration rate (6 to 7.2 L/h), it is apparent that renal tubular secretion plays an important role.

There is a simple, direct correlation between plasma concentrations of H2-receptor antagonists and the inhibition of gastric acid secretion. This implies a rapid equilibration between drug concentration in plasma and at the site of action, and a reversible drug-receptor interaction. Success in correlating the plasma concentration of H2-receptor antagonists and their pharmacological effects stems from reliable and precise measurement of both items.

Despite the heterogeneous nature of data sources, 50% inhibitory concentration (IC50) values for cimetidine, ranitidine, famotidine, nizatidine, etintidine and roxatidine obtained in vitro appear to be in good agreement with those determined in vivo. These results suggest that at an early stage of development of an H2-receptor antagonist, IC50 determined from in vitro studies may be useful as a first approximation to predict the clinically effective concentration of the new agent.

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References

  • Arrange JM, Garbarg M, Schwartz JC. Histamine synthesis and release in CNS: control by autoreceptors (H3). In Ganellin & Schwartz (Eds) Frontiers in histamine research, pp. 143–153, Pergamon Press, Oxford, 1985

    Google Scholar 

  • Ash ASF, Schild HO. Receptors mediating some actions of histamine. British Journal of Pharmacology 27: 427–439, 1966

    CAS  Google Scholar 

  • Berglindh T. Potentiation by carbacol and aminophylline of histamine-db-cAMP-induced parietal cell activity in isolated gastric gland. Acta Physiologica Scandinavica 99: 75–84, 1977

    Article  PubMed  CAS  Google Scholar 

  • Berstad A, Frislid K, Rydning A. Relationship between ranitidine plasma levels and reduction of post prandial intragastric acidities in healthy man. Scandinavian Journal of Gastroenterology 17: 109–112, 1982

    Article  PubMed  CAS  Google Scholar 

  • Bjorensson TD. Nomogram for drug dosage adjustment in patients with renal failure. Clinical Pharmacokinetics 11: 164–170, 1986

    Article  Google Scholar 

  • Black JW. The riddle of gastric histamine. In Yellin (Ed.) Histamine receptors, pp. 23–33, Medical & Scientific Books, New York, 1979

    Google Scholar 

  • Black JW, Duncan WAM, Durant JC, Ganellin CR, Parsons ME. Definition and antagonism of histamine H2-receptor. Nature 236: 385–390, 1972

    Article  PubMed  CAS  Google Scholar 

  • Black JW, Duncan WAM, Emmett JC, Ganellin CR, Hesselbo T, et al. Metiamide — an orally active histamine H2-receptor antagonist. Agents and Actions 3: 133–137, 1973

    Article  PubMed  CAS  Google Scholar 

  • Black JW, Leff P, Shankley NP. Further anomalous pKB values for histamine H2-receptor antagonists on the mouse isolated stomach assay. British Journal of Pharmacology 86: 581–587, 1985

    Article  PubMed  CAS  Google Scholar 

  • Bodemar G, Norlander B, Fransson L, Walan A. The absorption of cimetidine before and during maintenance treatment with cimetidine and the influence of a meal on the absorption of cimetidine: studies in patients with peptic ulcer disease. British Journal of Clinical Pharmacology 7: 23–31, 1979

    Article  PubMed  CAS  Google Scholar 

  • Bodemar G, Norlander B, Walan A. Diminished absorption of cimetidine caused by antacids. Lancet 1: 444–445, 1979

    Article  PubMed  CAS  Google Scholar 

  • Bodemar G, Norlander B, Walan A. Pharmacokinetics of cimetidine after single doses and during continuous treatment. Clinical Pharmacokinetics 6: 305–315, 1981

    Article  Google Scholar 

  • Bogues K, Dixon GT, Fowler P, Jenner WN, MacOnochie JG, et al. Pharmacokinetics and bioavailability of ranitidine in humans. British Journal of Pharmacology, 73: 275–276, 1981

    Google Scholar 

  • Bradshaw J, Brittain RT, Clitherow JW, Daly MJ, Jack D, et al. Ranitidine (AH 19065): a new potent selective histamine H2-receptor antagonist. British Journal of Pharmacology 68: 646, 1979

    Google Scholar 

  • Bradshaw J, Butcher ME, Clitherow JW. Aminoalkylfuran as H2-receptor antagonists. In Chemical regulation of biological mechanisms, Special Publications No. 42, Royal Society of Chemistry, London, 1982

    Google Scholar 

  • Brater DC, Meyers Jr WM, Dandelar KA, Pittman KA, Peterson W. Clinical pharmacology of etintidine in patients with duodenal ulcer. European Journal of Clinical Pharmacology 23: 495–500, 1982

    Article  PubMed  CAS  Google Scholar 

  • Bricker NS, Morrin PF, Kine SW. The pathologic physiology of chronic Bright’s disease: an expansion of the ‘intact nephron hypothesis’. American Journal of Medicine 28: 77–98, 1960

    Article  PubMed  CAS  Google Scholar 

  • Bright-Ashare T. Treatment of duodenal ulcer with enprostil, a prostaglandin E2 analogue. American Journal of Medicine 81: 64–68, 1986

    Article  Google Scholar 

  • Bright-Ashare P, Habte T, Yirgou B, Benjamin J. Prostaglandins, H2-receptor antagonists and peptic ulcer disease. Drugs 35 (Suppl.): 1–9, 1988

    Article  Google Scholar 

  • Brimblecombe RW, Duncan WAM, Durant GJ, Emmett JC, Ganellin CR, et al. Cimetidine: a non-thiourea H2-receptor antagonist. Journal of International Medical Research 3: 86–92, 1975

    CAS  Google Scholar 

  • Burgess E, Cutler RE, Blair AD. Cimetidine pharmacokinetics in hemodialysis patients and inhibition of creatinine secretion in healthy subjects. Clinical Pharmacology and Therapeutics 27: 247, 1980

    Google Scholar 

  • Burland WL, Darkin DW, Millis MW. Effects of antacids on absorption of cimetidine. Lancet 2: 965, 1976

    Article  PubMed  CAS  Google Scholar 

  • Burland WL, Duncan WAM, Hesselbo T, Mills JG, Sharpe PC. Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man. British Journal of Clinical Pharmacology 2: 481–486, 1975

    Article  PubMed  CAS  Google Scholar 

  • Buschauer A, Schunack W, Arrang JM, Garbarg M, Schwartz JC, et al. Histamine receptors. In Williams et al. (Eds) Receptor pharmacology and function, pp. 293–348, Marcel Dekker Inc, New York, 1988

    Google Scholar 

  • Callaghan JT, Bergstrom RF, Obermeyer BD, King EP, Offen WW. Intravenous nizatidine kinetics and acid suppression. Clinical Pharmacology and Therapeutics 37: 162–165, 1985

    Article  PubMed  CAS  Google Scholar 

  • Callaghan JT, Bergstrom RF, Rubin A, Chernish S, Crabtree R, et al. A pharmacokinetic profile of nizatidine in man. Scandinavian Journal of Gastroenterology 22 (Suppl. 136): 9–17, 1987

    Article  Google Scholar 

  • Campoli-Richards DM, Clissold SP. Famotidine: pharmacodynamic and pharmacokinetic properties and a preliminary review of its therapeutic use in peptic ulcer disease and Zollinger-Ellison syndrome. Drugs 32: 197–221, 1986

    Article  PubMed  CAS  Google Scholar 

  • Cavanagh R, Usakewicz JJ, Buyniski JP. A comparison of some of the pharmacological properties of etintidine, a new H2-receptor antagonist, with those of cimetidine, ranitidine, and tiotidine. Journal of Pharmacology and Experimental Therapeutics 224: 171–179, 1983

    PubMed  CAS  Google Scholar 

  • Chand N, Eyre P. Classification and biological distribution of histamine receptor sub-types. Agents and Actions 5: 277–295, 1975

    Article  PubMed  CAS  Google Scholar 

  • Chau NP, Zech PY, Pozet N, Hadj-Aissa A. Ranitidine kinetics in normal subjects. Clinical Pharmacology and Therapeutics 31: 770–774, 1982

    Article  PubMed  CAS  Google Scholar 

  • Cheret AM, Pignal F, Lewin MJM. Effects of H2-receptor antagonists, cimetidine, ranitidine and ICI 125,211 on histaminestimulated adenylate cyclase activity in guinea pig gastric mucosa. Molecular Pharmacology 20: 326–330, 1981

    PubMed  CAS  Google Scholar 

  • Code CF. Histamine receptors and gastric secretion. In Ganellin & Parsons (Eds) Pharmacology of histamine receptors, pp. 217–235, Wright PSG, London, 1982

    Google Scholar 

  • Collins JD, Pidgen AW. Pharmacokinetics of roxatidine in healthy volunteers. Drugs 35 (Suppl. 3): 41–47, 1988

    Article  PubMed  CAS  Google Scholar 

  • Cunningham F, Nanavaty M, Fischer J, Danziger L, Rodvold K, et al. Pharmacokinetic (PK)/Pharmacodynamic (PD) model for nizatidine (N) effect on basal gastric acid (BGA) output. Clinical Pharmacology and Therapeutics 45: 141, 1989

    Google Scholar 

  • Dammann HG, Muller P, Simon B. 24-Hour intragastric acidity and single night-time dose of three H2-blockers. Lancet 2: 1078, 1983

    Article  PubMed  CAS  Google Scholar 

  • Donnelly R, Meredith PA, Elliott HL. Pharmacokinetic-pharmacodynamic relationships of α-adrenoceptor antagonists. Clinical Pharmacokinetics 17: 264–274, 1989

    Article  PubMed  CAS  Google Scholar 

  • Drayer D, Romankiewicz J, Lorenzo B, Reidenberg MM. Age and renal clearance of cimetidine. Clinical Pharmacology and Therapeutics 31: 45–50, 1982

    Article  PubMed  CAS  Google Scholar 

  • Edmonds ME, Ashford RFU, Byenner MK, Saunders A. Cimetidine: does neurotoxicity occur? Report of three cases. Journal of the Royal Society of Medicine 72: 172–175, 1979

    PubMed  CAS  Google Scholar 

  • Eshelman FN, Plachetka JR, Brown BCP. Effect of antacid and anticholinergic medication on ranitidine absorption. Clinical Pharmacology and Therapeutics 33: 216 (111D), 1983a

    Google Scholar 

  • Eshelman FN, Plachetka JR, Brown BCP. Bioavailability and tolerance of repeated intramuscular infections of ranitidine. Clinical Pharmacology and Therapeutics 33: 251 (C10), 1983b

    Google Scholar 

  • Frislid K, Berstad A. High dose of antacid reduce bioavailability of ranitidine. British Medical Journal 286: 1358, 1983

    Article  PubMed  CAS  Google Scholar 

  • Ganellin CR. Imidazole tautomerism of histamine derivatives. In Bergman & Pullman (Eds) Molecular and quantum pharmacology, pp. 43–53, D. Reidel Publishing Company, Dordrecht, 1974

    Chapter  Google Scholar 

  • Ganellin CR. A survey of recently described H2-receptor histamine antagonists. In Ganellin & Schwartz (Eds) Frontiers in histamine research, pp. 47–59, Pergamon Press, Oxford, 1985

    Google Scholar 

  • Garg DC, Weidler DJ, Eshelman FN. Ranitidine bioavailability and kinetics in normal male subjects. Clinical Pharmacology and Therapeutics 33: 445–452, 1983

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi M, Levy G, Hayton W. Kinetics of tubocurarine elimination and neuromuscular blocking effect in man. Anesthesiology 36: 213–218, 1972

    Article  PubMed  CAS  Google Scholar 

  • Grahneń A, Von Bahr C, Lindström B, Rosén A. Bioavailability and pharmacokinetics of cimetidine. European Journal of Clinical Pharmacology 16: 335–340, 1979

    Article  PubMed  Google Scholar 

  • Guay DRP, Matzko GR, Bockbrader HN, Danick J. Comparison of bioavailability and pharmacokinetics of cimetidine in subjects with normal and impaired renal function. Clinical Pharmacy 2: 157–162, 1983

    PubMed  CAS  Google Scholar 

  • Gugler R, Brand M, Somogyi A. Impaired cimetidine absorption by antacids and metoclopramide. European Journal of Clinical Pharmacology 20: 225–228, 1981a

    Article  PubMed  CAS  Google Scholar 

  • Gugler R, Fuchs G, Dieckmann M, Somogyi A. Cimetidine plasma concentration-response relationships. Clinical Pharmacology and Therapeutics 29: 744–748, 1981b

    Article  PubMed  CAS  Google Scholar 

  • Gugler R, Müller-Liebenau B, Somogyi A. Altered disposition and bioavailability of cimetidine in liver cirrhotic patients. British Journal of Clinical Pharmacology 14: 421–429, 1982

    Article  PubMed  CAS  Google Scholar 

  • Gustavsson S, Marrdh S, Norberg L, Nyren O, Wollert S. Omeprazole, cimetidine and ranitidine: inhibition of acid production in isolated human parietal cells. Scandinavian Journal of Gastroenterology 20: 917–921, 1985

    Article  PubMed  CAS  Google Scholar 

  • Harada M, Terai M, Maeno H. Effect of a new potent H2-receptor antagonist, 3 ((2-((diaminomethylene)amino)-4-thiazolyl)methyl) thio-N2-sulfamoylpropionamidine (YM-11170) on gastric muscosal histamine-sensitive adenylate cyclase from guinea pig. Biochemical Pharmacology 32: 1635–1640, 1983

    Article  PubMed  CAS  Google Scholar 

  • Henn RM, Isenberg JI, Maxwell V, Sturdevant RAL. Inhibition of gastric acid secretion by cimetidine in patients with duodenal ulcer. New England Journal of Medicine 293: 371–375, 1975

    Article  PubMed  CAS  Google Scholar 

  • Holloway RH, Kuljian B, Eshelman F, McCallum RW. Effects of ranitidine and of cimetidine on pentagastrin-stimulated gastric acid secretion. Clinical Pharmacology and Therapeutics 35: 203–207, 1984

    Article  PubMed  CAS  Google Scholar 

  • Howden CW, Jones DB, Hunt RH. Nocturnal doses of H2-receptor antagonists for duodenal ulcer. Lancet 1: 647–648, 1985

    Article  PubMed  CAS  Google Scholar 

  • Huang SM, Marlott TB, Weintraub HS, Arnold JD, Boccagno J. Single-dose and multiple-dose pharmacokinetics of etintidine in healthy volunteers. European Journal of Clinical Pharmacology 34: 101–104, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ishizaki T, Hirayama J, Tawara K, Nakaya H, Sato M, et al. Pharmacokinetics and pharmacodynamics in young normal and elderly hypertensive subjects: a study using sotalol as a model drug. Journal of Pharmacology and Experimental Therapeutics 212: 173–181, 1980

    PubMed  CAS  Google Scholar 

  • Johnson CL. Histamine receptors and cyclic nucleotides. In Ganellin & Parsons (Eds) Pharmacology of histamine receptors, pp. 146–216, Weight PSG, London, 1982

    Google Scholar 

  • Jönsson KA, Erikssen S-E, Kagev I, Norlander B, Bodemar G, et al. Cimetidine but not oxmetidine, penetrates into cerebrospinal fluid after a single intravenous dose. British Journal of Clinical Pharmacology 14: 815–819, 1982

    Article  PubMed  Google Scholar 

  • Kagevi I, Thorhallson E, Wahlby L. CSF concentration of famotidine. British Journal of Clinical Pharmacology 24: 849–850, 1987

    Article  PubMed  CAS  Google Scholar 

  • Kaojarern S, Feldman M, Richardson CT, Brater DC. Tiotidine and cimetidine kinetics and dynamics. Clinical Pharmacology and Therapeutics 29: 198–202, 1981

    Article  PubMed  CAS  Google Scholar 

  • Karppanen HO, Westermann E. Increased production of cyclic AMP in gastric tissues by stimulation of histamine (H2)-receptors. Naunyn-Schmiedeberg’s Archives of Pharmacology 279: 83–87, 1973

    Article  PubMed  CAS  Google Scholar 

  • Kimelblatt BJ, Cerra FB, Caller G, Berg MJ, McMillen MA, et al. Dose and serum concentration relationships in cimetidine-associated mental confusion. Gastroenterology 78: 791–795, 1980

    PubMed  CAS  Google Scholar 

  • Knadler MP, Bergstrom RF, Callaghan JT, Rubin A. Nizatidine, an H2-blocker: its metabolism and disposition in man. Drug Metabolism and Disposition 14: 175–182, 1986

    PubMed  CAS  Google Scholar 

  • Knadler MP, Rubin A, Bergstrom RF, Callaghan JT. Effects of gelusil (g), charcoal (c) and propantheline (p) on the bioavailability of the H2-blocker nizatidine (n). Pharmacologist 26: 236, 1984

    Google Scholar 

  • Kroemer H, Klotz U. Pharmacokinetics of famotidine in man. International Journal of Clinical Pharmacology, Therapy and Toxicology 25: 458–463, 1987

    CAS  Google Scholar 

  • Labs RA. Interaction of roxatidine acetate with antacids, food and other drugs. Drugs 35 (Suppl. 3): 82–89, 1988

    Article  PubMed  CAS  Google Scholar 

  • Lameire N, Rosenkranz B, Maass L, Brockmeier D. A pharmacokinetic study of roxatidine acetate in chronic renal failure. Drugs 35 (Suppl. 3): 48–52, 1988

    Article  PubMed  Google Scholar 

  • Larsson R, Erlanson P, Bodemar G, Walan A, Bertler A, et al. The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function. British Journal of Clinical Pharmacology 13: 163–170, 1982

    Article  PubMed  CAS  Google Scholar 

  • Lassman HB, Ho I, Puri SK, Sabo R, Scheffler MR. The pharmacodynamics and pharmacokinetics of multiple doses of the new H2-receptor antagonist, roxatidine acetate, in healthy men. Drugs 35:(Suppl. 3): 53–64, 1988

    Article  PubMed  CAS  Google Scholar 

  • Lebert PA, Mahon WA, MacLeod SM, Soldin SJ, Fenje P, et al. Ranitidine kinetics and dynamics: I. Oral dose studies. Clinical Pharmacology and Therapeutics 30: 539–544, 1981

    Article  PubMed  CAS  Google Scholar 

  • Lin JH, Chremos AN, Kanovsky SM, Schwartz KC, Yeh KC, et al. Effects of antacids and food on absorption of famotidine. British Journal of Clinical Pharmacology 24: 551–553, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Lin JH, Chremos AN, Yeh KC, Antonello J, Hessey II GA. Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man. European Journal of Clinical Pharmacology 34: 41–46, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Lin TM, Evans DC, Warrick MW, Pioch RP, Ruffolo RR. Nizatidine, a new specific H2-receptor antagonist. Gastroenterology 84: 1231, 1983

    Google Scholar 

  • Lin TM, Evans DC, Warrick MW, Pioch RP. Action of nizatidine, a selective histamine H2-receptor antagonist, on gastric acid secretion in dogs, rats and frogs. Journal of Pharmacology and Experimental Therapeutics 239: 406–410, 1986

    PubMed  CAS  Google Scholar 

  • Lin JH, Hayashi M, Awaza S, Hanano M. Correlation between in vitro and in vivo drug metabolism rate: oxidation of ethoxybenzamide in rat. Journal of Pharmacokinetics and Biopharmaceutics 6: 327–337, 1978

    PubMed  CAS  Google Scholar 

  • Lin JH, Lin T-H, Ulm EH. Renal handling of drugs in renal failure: evaluation of etiologically different models of acute renal failure in rats. Pharmaceutical Research 5 (Suppl.): S–188, 1988b

    Google Scholar 

  • Lin JH, Los LE, Ulm EH, Duggan DE. Urinary excretion kinetics of famotidine in rats. Drug Metabolism and Disposition 15: 212–216, 1987a

    PubMed  CAS  Google Scholar 

  • Lin JH, Los LE, Ulm EH, Duggan DE. Kinetic studies on the competition between famotidine and cimetidine in rats: evidence of multiple renal secretory systems for organic cations. Drug Metabolism and Disposition 16: 52–56, 1988c

    PubMed  CAS  Google Scholar 

  • Lin JH, Sugiyama Y, Awaza S, Hanano M. Physiological pharmacokinetics of ethoxybenzamide based on biochemical data obtained in vitro as well as on physiological data. Journal of Pharmacokinetics and Biopharmaceutics 10: 649–661, 1982

    PubMed  CAS  Google Scholar 

  • Longstreth GF, Go VLM, Malagelada JR. Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer. New England Journal of Medicine 294: 801–804, 1976

    Article  PubMed  CAS  Google Scholar 

  • Martin LE, Bell JA, Carey PF, Dallas FAA, Dixon GT, et al. A review of the pharmacokinetics and metabolism of ranitidine in animals and man. In Misiewicz & Wormsley (Eds) The clinical use of ranitidine, Medicine Publishing Foundation Series 5, pp. 23–31, Medicine Publishing Foundation, Oxford, 1982

    Google Scholar 

  • McDevitt DG, Shand DG. Plasma concentrations and the time-course of beta block due to propranolol. Clinical Pharmacology and Therapeutics 18: 708–713, 1975

    PubMed  CAS  Google Scholar 

  • McFadyen ML, Folb PI, Miller R, Keeton GR, Marks IN. Pharmacokinetics of ranitidine in patients with chronic renal failure. European Journal of Clinical Pharmacology 25: 347–351, 1983

    Article  PubMed  CAS  Google Scholar 

  • McNeil JJ, Mihaly GW, Anderson A, Marshall AW, Smallwood RA, et al. Pharmacokinetics of the H2-receptor antagonists of ranitidine in man. British Journal of Clinical Pharmacology 12: 411–415, 1981

    Article  PubMed  CAS  Google Scholar 

  • Mignon M, Chau NP, Nguyen-Phuoc BK, Saurage M, Leguy F, et al. Ranitidine, effects on meal-induced gastric secretion: oral pharmacokinetics and plasma concentration. British Journal of Clinical Pharmacology 14: 187–193, 1982

    Article  PubMed  CAS  Google Scholar 

  • Mihaly GW, Marino AT, Webster LK, Jones DB. High doses of antacid (Mylanta II) reduces bioavailability of ranitidine. British Medical Journal 285: 998–999, 1982

    Article  PubMed  CAS  Google Scholar 

  • Miwa M, Tani N, Miwa T. Inhibition of gastric secretion by a new H2-receptor antagonist YM-11170 in healthy subjects. International Journal of Clinical Pharmacology, Therapy and Toxicology 22: 214–217, 1984

    CAS  Google Scholar 

  • Necciari J, Mery D, Garriot P, Escourrou J, Cauteels W. Pharmacokinetics of CM57755, a new histamine H2-receptor antagonist, after single oral dose in man. International Journal of Clinical Pharmacology and Research 6: 457–465, 1985

    Google Scholar 

  • Nishihara S, Tanaka A, Imazono Y, Misawa T, Ibayashi H. Effect of a new H2-receptor antagonist (BL-5641) on [3H]-cimetidine binding and histamine-stimulated cAMP production in isolated guinea pig gastric glands. Igaku no Ayumi 134: 283–284, 1985

    CAS  Google Scholar 

  • Nishihara S, Tanaka A, Tazoe A, Yoshida K, Misawa T, et al. Inhibitory effect of etintidine (BL-5641), a new type of H2-receptor antagonist, on binding of [3H]-cimetidine to plasma membrane and histamine-stimulated cellular cAMP production in isolated guinea pig gastric glands. Gastroenterologica Japonica 21: 106–111, 1986

    CAS  Google Scholar 

  • Okolicsanyi L, Venuti M, Orlando R, Lirussi F, Nassuato G, et al. Oral and intravenous pharmacokinetics of cimetidine in liver cirrhosis. International Journal of Clinical Pharmacology, Therapy and Toxicology 20: 482–487, 1982

    CAS  Google Scholar 

  • Pang KS, Rowland M, Tozer TN. In vivo evaluation of Michaelis-Menten constants of hepatic drug-eliminating systems. Drug Metabolism and Disposition 6: 197–200, 1978

    PubMed  CAS  Google Scholar 

  • Paringer L, Berk A. Cost of illness and disease: fiscal year, 1975. Report no. 2, Contract 1-OD-5-2121, Washington DC, Public Services Laboratory, Georgetown University, 1977

    Google Scholar 

  • Peden NR, Richards DA, Saunders JHB, Wormsley KG. Pharmacologically effective plasma concentrations of ranitidine. Lancet 2: 199–200, 1979

    Article  PubMed  CAS  Google Scholar 

  • Poli E, Medici D, Contini GA, Bertaccini G. Effect of mifentidine on histamine-stimulated human atrium ‘in vitro’: comparison with ranitidine and cimetidine. Archives of Internationales de Pharmacodynamie et de Therapie 273: 221–225, 1985

    CAS  Google Scholar 

  • Popielski L. B-Imidazolylathylamin und die Organextrakte: I. B-Imidazolylathylamin als machtigen Erreger der Magendrusen. Pflgers Archiv für die gesante Physiologie des Menschen und der Tiere 178: 214–236, 1920

    Article  CAS  Google Scholar 

  • Pounder RE, Williams JG, Russell RCG, Milton-Thompson GJ, Misiewicz JJ. Inhibition of food-stimulated gastric acid secretion by cimetidine. Gut 17: 161–168, 1976

    Article  PubMed  CAS  Google Scholar 

  • Rowley-Jones D, Grainger E. Cimetidine by intramuscular administration: efficacy and safety. World Conference on Clinical Pharmacology and Therapeutics, London, 1980, Abstract no. 399, MacMillan, London, 1980

    Google Scholar 

  • Rune SJ, Hesselfeldt P, Larsen NE. Clinical and pharmacological effectiveness of cimetidine in duodenal ulcer patients. Scandinavian Journal of Gastroenterology 14: 489–492, 1979

    CAS  Google Scholar 

  • Ryan JR, Chremos AN, Vargas R, Mantell G, Johnson GL, et al. The effect of various dose regimens of famotidine on basal nocturnal and meal-stimulated gastric secretion. Clinical Pharmacology and Therapeutics 42: 225–231, 1987

    Article  PubMed  CAS  Google Scholar 

  • Savarino V, Picciotto A, Magnolia MR, Scalabrini P, Mela G, et al. Single bedtime dose of famotidine: assessment of its anti-secretary action by 24-hour intragastric pH monitoring. Journal of Clinical Pharmacology 27: 790–793, 1987

    PubMed  CAS  Google Scholar 

  • Schentag JJ, Cerra FB, Calleri GM, Leising ME, French MA, et al. Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients. Clinical Pharmacology and Therapeutics 29: 737–743, 1981

    Article  PubMed  CAS  Google Scholar 

  • Schepp W, Miederer SE, Ruoff HJ. Effects of hormones (calcitonin, GIP) and pharmacological antagonists (ranitidine and famotidine) on isolated rat parietal cells. Regulatory Peptides 12: 297–308, 1985

    Article  PubMed  CAS  Google Scholar 

  • Scholtholt J, Bickel M, Herling AW. A review of the animal pharmacology of roxatidine acetate. Drugs 35 (Suppl.): 30–40, 1988

    Article  PubMed  CAS  Google Scholar 

  • Sewing K-Fr, Beil W, Hannemann H. Comparative pharmacology and histamine H2-receptor antagonists. Drugs 35 (Suppl. 3): 25–29, 1988

    Article  PubMed  CAS  Google Scholar 

  • Shepherd AMM, Stewart WK, Wormsley KG. Peptic ulceration in chronic renal failure. Lancet 1: 1357–1359, 1973

    Article  PubMed  CAS  Google Scholar 

  • Shepherd-Rose AJ, Pendleton RG. Studies on the H2-receptor antagonism of MK-208 in isolated rabbit gastric glands. European Journal of Pharmacology 106: 423–426, 1985

    Article  Google Scholar 

  • Smith SE. Duration of action of beta-blocking drugs. British Medical Journal 2: 715, 1973

    Article  Google Scholar 

  • Somogyi A, Rohner HG, Gugler R. Pharmacokinetics and bio-availability of cimetidine in gastric and duodenal ulcer patients. Clinical Pharmacokinetics 5: 84–94, 1980

    Article  PubMed  CAS  Google Scholar 

  • Somogyi A, Thielscher S, Gugler R. Influence of phenobarbital treatment of cimetidine kinetics. European Journal of Clinical Pharmacology 19: 343–347, 1981

    Article  PubMed  CAS  Google Scholar 

  • Sonne J, Poulsen HE, Dossing M, Larsen NE, Andreasen PB. Cimetidine clearance and bioavailability in hepatic cirrhosis. Clinical Pharmacology and Therapeutics 29: 191–197, 1981

    Article  PubMed  CAS  Google Scholar 

  • Sung CP, Jenkis BC, Burns LR, Hackney V, Spenney JG, et al. Adenyl and guanyl cyclase in rabbit gastric mucosa. American Journal of Physiology 225: 1359–1363, 1973

    PubMed  CAS  Google Scholar 

  • Tanaka A, Nishihara S, Misawa T, Ibayashi H. Effects of H2-receptor antagonists on [3H]-cimetidine binding and hist-amine-stimulation of cellular cAMP in isolated guinea pig gastric glands. Japanese Journal of Pharmacology 45: 97–105, 1987

    Article  PubMed  CAS  Google Scholar 

  • Tanaka A, Nishihara S, Misawa T, Yamauchi T, Ibayashi H. Effect of H2-receptor antagonists on [3H]-cimetidine binding and histamine-stimulated cAMP production in isolated gastric glands from guinea pig stomach. Igaku no Ayumi 130: 433–434, 1984

    CAS  Google Scholar 

  • Taylor DC, Cresswell PR, Bartlett DC. The metabolism and elimination of cimetidine, a histamine H2-receptor antagonist, in the rat, dog and man. Drug Metabolism and Disposition 6: 21–30, 1978

    PubMed  CAS  Google Scholar 

  • Van Ginneken CAM. Kinetics of drug-receptor interaction. In Van Rossum (Ed.) Kinetics of drug action, pp. 257–411, Springer-Verlag, Berlin, Heidelberg, New York, 1977

    Google Scholar 

  • Van Hecken AM, Tjandramaga TB, Mullie A, Verbesselt R, DeSchepper PJ. Ranitidine: single dose pharmacokinetics and absolute bioavailability in man. British Journal of Clinical Pharmacology 14: 195–200, 1982

    Article  PubMed  Google Scholar 

  • Vargas R, Ryan J, McMahon FG, Regel G, Offen WW, et al. Pharmacokinetics and pharmacodynamics of oral nizatidine. Journal of Clinical Pharmacology 28: 71–75, 1988

    PubMed  CAS  Google Scholar 

  • Von Haunalter G, Chandler VV. Cost of ulcer disease in the United States. Stanford Research Institute Project 5894, Stanford, California, 1977

  • Walkenstein SS, Dubb JW, Rondolph WC, Westlake WJ, Stote RM, et al. Bioavailability of cimetidine in man. Gastroenterology 74: 360–365, 1978

    PubMed  CAS  Google Scholar 

  • Walt RP, LaBrooy SJ, Avgerinos A, Oehr T, Riley A, et al. Investigations 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): 19–23, 1981

    CAS  Google Scholar 

  • Weiner IM, Roth L. Renal excretion of cimetidine. Journal of Pharmacology and Experimental Therapeutics 216: 516–520, 1981

    PubMed  CAS  Google Scholar 

  • Yeh KC, Chremos AN, Lin JH, Constanzer ML, Kanovsky SM, et al. Single-dose pharmacokinetics and bioavailability of famotidine in man: results of multicenter collaborative studies. Biopharmaceutics and Drug Disposition 8: 549–560, 1987

    Article  CAS  Google Scholar 

  • Young CJ, Daneshmend TK, Roberts CJC. Effects of cirrhosis and ageing on the elimination and bioavailability of ranitidine. Gut 23: 819–823, 1982

    Article  PubMed  CAS  Google Scholar 

  • Ziemniak JA, Welage LS, Schentag JJ. Cimetidine and ranitidine. In Evans et al. (Eds) Applied pharmacokinetics, 2nd ed., pp. 782–825, Applied Therapeutics, Inc., Spokane, 1986

    Google Scholar 

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  1. Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania, USA

    Jiunn H. Lin

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Lin, J.H. Pharmacokinetic and Pharmacodynamic Properties of Histamine H2-Receptor Antagonists. Clin. Pharmacokinet. 20, 218–236 (1991). https://doi.org/10.2165/00003088-199120030-00004

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