Summary
Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17β-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A.
There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days.
No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests.
Similar content being viewed by others
References
Bank S, Barbezat GO, Vinik AI, Helman C (1977) Serum gastrin levels before and after 6 weeks of cimetidine therapy in patients with duodenal ulcer. Digestion 15: 157–161
Barber SG (1979) Male sexual dysfunction and cimetidine. Br Med J 1: 1147
Bateson MC, Browning MCK, Maconnachie A (1977) Galactorrhoea with cimetidine. Lancet 2: 247–248
Biagi P, Galli M, Brettoni A, Rizzo AA, Massafra C (1984) Variazioni della prolattina sierica in corso di trattamento short-term con cimetidina e ranitidina in soggetti ulcerosi di sesso maschile. Clin Ter 109: 345–348
Bianchi Porro G, Ragni G, Ruspa M, Petrillo M, Barattini G (1985) Long-term treatment with cimetidine does not essentially affect the hypothalamic-pituitary-gonadal axis in man. Hepatogastroenterology 32: 77–80
Bohnet HG, Greiwe M, Hanker JP, Aragona C, Schneider HPG (1978) Effects of cimetidine on prolactin, LH and sex steroid secretion in male and female volunteers. Acta Endocrinol 88: 428–434
Brassinne A, Dresse A, Basilisco G, Manara L (1987) Inhibition of pentagastrin-stimulated gastric acid secretion and plasma levels of the new histamine H2-receptor antagonist ramixotidine dihydrochloride (CM 57755) in human volunteers. Eur J Clin Pharmacol 32: 467–470
Burland WL, Gleadle RI, Lee RM, Rowley-Jones D (1979) Prolactin responses to cimetidine. Br J Clin Pharmacol 7: 19–21
Daubresse JC, Meunier JC, Ligny G (1978) Plasma prolactin and cimetidine. Lancet 1: 99
Delitala G, Devilla L, Pende A, Canessa A (1982) Effects of the H2-receptor antagonist ranitidine on anterior pituitary hormone secretion in man. Eur J Clin Pharmacol 22: 207–211
Delitala G, Stubbs WA, Wass JAH, Yeo T, Jones A, Williams S, Besser GM, La Brooy SJ, Misiewicz JJ (1978) Hypothalamicpituitary effects of cimetidine. Lancet 2: 1054–1055
Delle Fave GF, Tamburrano G, de Magistris L, Natoli C, Santoro ML, Carratu R, Torsoli A (1977) Gynaecomastia with cimetidine. Lancet 1: 1319
Elder JB (1985) Inhibition of acid and gastric carcinoids. Gut 26: 1279–1283
Forrest JAH, Fettes MR, McLoughlin GP, Heading RC (1979) Effect of long-term cimetidine on gastric acid secretion, serum gastrin, and gastric emptying. Gut 20: 404–407
Frantz AG (1978) Prolactin. N Engl J Med 298: 201–207
Frislid K, Berstad A (1986) Effect of ranitidine on meal-induced gastric pepsin and acid secretion and the influence of adding ethanol to the meal. Scand J Gastroenterol 21: 123–128
Hall WH (1976) Breast changes in males on cimetidine. N Engl J Med 295: 841
Hansky J, Stern AI, Korman MG, Waugh J (1979) Effects of long-term cimetidine on serum gastrin in duodenal ulcer. Dig Dis Sci 24: 468–470
Healy DL, Burger HG, Korman MG, Stern A (1979) Long-term cimetidine does not alter serum prolactin. Horm Res 11: 53–55
Hirschowitz BI, Danilewitz M, Molina E (1982) Inhibition of basal acid, chloride, and pepsin secretion in duodenal ulcer by graded doses of ranitidine and atropine with studies of pharmacokinetics of ranitidine. Gastroenterology 82: 1314–1326
Jensen RT, Collen MJ, Pandol SJ, Allende HD, Raufman JP, Bissonnette BM, Duncan WC, Durgin PL, Gillin JC, Gardner JD (1983) Cimetidine-induced impotence and breast changes in patients with gastric hypersecretory states. N Engl J Med 308: 883–887
Kleinberg DL, Noel GL, Frantz AG (1977) Galactorrhea: A study of 235 cases, including 48 with pituitary tumors. N Engl J Med 296: 589–600
Konturek SJ, Obtulowicz W, Kwiecien N, Sito E, Mikos E, Olesky J (1980) Comparison of ranitidine and cimetidine in the inhibition of histamine, sham-feeding, and meal-induced gastric secretion in duodenal ulcer patients. Gut 21: 181–186
Koop H, Arnold R, Creutzfeldt W (1984) Pancreatic polypeptide and gastrin release during sham feeding in man. Digestion 30: 47–52
Lavezzo A, Manzoni L, Bianchetti A, Manara L (1986) Inhibition of dimaprit- and pentagastrin-induced gastric acid secretion in cats by the new histamine H2-antagonist, CM 57755. J Pharm Pharmacol 38: 853–856
Leslie GB, Walker TF (1977) A toxicological profile of cimetidine. In: Burland WL, Simkins MA (eds) Proceedings of the second international symposium on histamine H2-receptor antagonists. Excerpta Medica, Amsterdam Oxford, pp 24–33
Longstreth GF, Go VLW, Malagelada JR (1976) Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer. N Engl J Med 294: 801–804
Mahachai V, Walker K, Jamali F, Navert H, Cook D, Symes A, Thomson ABR (1984) Comparative effects of two cimetidine regimens on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer. Clin Ther 6: 259–281
Majumdar SK, Thomson AD, Shaw GK (1978) Cimetidine and serum prolactin. Br Med J 1: 409
Mignon M, Sauvage M, Leroux S, Bonfils S (1980) Effet de doses variées de ranitidine sur la sécrétion acide, la vidange gastrique et la gastrine sérique lors d'un repas test chez l'homme. Gastroenterol Clin Biol 4: 158 A
Mohammed R, Holden RJ, Hearns JB, McKibben BM, Buchanan KD, Crean GP (1983) Effects of eight weeks' continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion, and fasting serum gastrin. Gut 24: 61–66
Müller P, Dammann HG, Simon B (1985) Human acid secretion during and after 18 days' treatment with omeprazole. Ital J Gastroenterol 17: 96–97
Nelis GF, Van de Meene JGC (1980) Comparative effect of cimetidine and ranitidine on prolactin secretion. Postgrad Med J 56: 478–480
Paulsen CA, Enzmann GD, Bremner WJ, Perrin EB, Rogers BJ (1983) Effects of cimetidine on reproductive function in men. In: Cohen S (ed) Update: H2-receptor antagonists. Biomedical Information Corporation, pp 169–178
Peden NR, Cargill JM, Browning MCK, Saunders JHB, Wormsley KG (1979) Male sexual dysfunction during treatment with cimetidine. Br Med J 1: 659
Perret G, Hugues JN, Louchahi M, Varoquaux O, Modigliani E (1986) Effect of a short-term oral administration of cimetidine and ranitidine on the basal and thyrotropin-releasing hormone-stimulated serum concentrations of prolactin, thyrotropin and thyroid hormones in healthy volunteers. A doubleblind cross-over study. Pharmacology 32: 101–108
Petrillo M, Prada A, Bianchi Porro G, Bevilacqua M, Raggi V, Norbiato G (1977) Plasma-prolactin and cimetidine. Lancet 2: 761
Richardson CT, Walsh JH, Hicks MI (1976) The effect of cimetidine, a new histamine H2-receptor antagonist on meal-stimulated acid secretion, serum gastrin and gastric emptying in patients with duodenal ulcer. Gastroenterology 71: 19–23
Rowley-Jones D (1978) Cimetidine and serum-prolactin. Lancet 2: 635
Sharpe PC, Melvin MA, Mills JG, Burland WL, Groom GV (1980) Prolactin responses to histamine H2-receptor antagonists. Acta Endocrinol 95: 308–313
Siewert R, Lepsien G, Arnold R, Creutzfeldt W (1977) Effect of cimetidine on lower esophageal sphincter pressure, intragastric pH and serum levels of immunoreactive gastrin in man. Digestion 15: 81–85
Smout AJPM, Bogaard WJ, Van Hattum J, Akkermans LMA (1985) Effects of cimetidine and ranitidine on interdigestive and postprandial lower esophageal spincter pressures and plasma gastrin levels in normal subjects. Gastroenterology 88: 557–563
Soldani G, Mengozzi G, Polloni A (1986) Effects of CM 57755A on gastric acid secretion and gastrin release in the dog. Dig Dis Sci 31 [Suppl]: 394S
Spence RW, Celestin LR (1979) Gynaecomastia associated with cimetidine. Gut 20: 154–157
Spiegel AM, Lopatin R, Peikin S, McCarthy D (1978) Serumprolactin in patients receiving chronic oral cimetidine. Lancet 1: 881
Spona J, Weisz W, Rüdiger E, Hentschel E, Schütze K, Reichel W, Kerstan E, Wewalka F, Lochs H (1981) Hormone serum levels during oral cimetidine treatment of patients with peptic ulcers. Hepatogastroenterology 28: 165–168
Stubbs WA, Delitala G, Besser GM, Edwards CRW, Labrooy S, Taylor R, Misiewicz JJ, Alberti KGMM (1983) The endocrine and metabolic effects of cimetidine. Clin Endocrinol 18: 167–178
Thomas JM, Misiewicz G (1984) Histamine H2-receptor antagonists in the short- and long-term treatment of duodenal ulcer. In: Isenberg JI, Johannson C (eds) Clinics in gastroenterology. Peptic ulcer disease. Saunders, London Philadelphia Toronto, pp 501–541
Van Thiel DH, Gavaler JS, Smith WI Jr, Paul G (1979) Hypothalamic-pituitary-gonadal dysfunction in men using cimetidine. N Engl J Med 300: 1012–1015
Von Kleist D, Gräf KJ, Dougherty FC, Hampel KE (1981) Effects of cimetidine and ranitidine on gastric transmural potential difference and on prolactin secretion in man. Hepatogastroenterology 28: 210–212
Wallin L, Madsen T, Brandsborg M, Brandsborg O, Larsen NE (1979) The influence of cimetidine on basal gastro-oesophageal sphincter pressure, intragastric pH, and serum gastrin concentration in normal subjects. Scand J Gastroenterol 14: 349–353
White MC, Gore M, Jewell DP (1979) Endocrine function after cimetidine. N Engl J Med 301: 502
Wilson JA, Johnston D, Penston J, Wormsley KG (1986) Gastric inhibitory effects of CM 57755. Eur J Clin Pharmacol 30: 33–36
Winters SJ, Banks JL, Loriaux DL (1979) Cimetidine is an anti-androgen in the rat. Gastroenterology 76: 504–508
Wolfe MM (1979) Impotence on cimetidine treatment. N Engl J Med 300: 94
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Colle, M., Ruedas, E., Cazenave, J. et al. Plasma prolactin, sex steroids and gastrin in human volunteers treated for 2 weeks with therapeutic doses of cimetidine or the new histamine H2-receptor antagonist ramixotidine (CM 57755A). Eur J Clin Pharmacol 35, 529–534 (1988). https://doi.org/10.1007/BF00558249
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00558249