Summary
The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
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References
Alván, G., Orme, M., Bertilsson, L., Ekstrand, R., Palmer, L.: Pharmacokinetics of indometacin. Clin. Pharmacol. Ther.18, 364–373 (1975)
Binder, H., Cocco, A., Crossley, R. J., Finkelstein, W., Font, R., Friedman, G., Groarke, J., Huges, W., Johnsson, A. F., McGuigan, J. E., Summer, R., Vlahcevic, R., Wilson, E. C., Winship, D. H.: Cimetidine in the treatment of duodenal ulcer. A multicenter double blind study. Gastroenterology74, 380–387 (1978)
Bodemar, G., Norlander, B., Fransson, L., Wahlan, A.: The influence of a meal and antacids on cimetidine absorption in patients with peptic ulcer disease. Scand. J. Gastroenterol.12, Suppl. 45, 12 (1977)
Bradley, S. E., Ingelfinger, F. J., Bradley, G. P., Currey, J. J.: The estimation of hepatic blood flow in man. J. Clin. Invest.24, 890–897 (1945)
Burland, W. L., Simkins, A. M.: Cimetidine. Proceedings of the Second International Symposium on Histamine H2-Receptor Antagonists. Amsterdam: Excerpta Medica 1977
Burland, W. L., Duncan, W. A. M., Hesselbo, T., Mills, J. G., Sharpe, P. C., Haggie, S. J., Wyllie, J. H.: Pharmacological evaluation of cimetidine. A new histamine H2-receptor antagonist, in healthy man. Br. J. Pharmacol.2, 481–486 (1975)
Ekstrand, J., Ehrnebo, M., Boréus, L. O.: Fluoride bioavailability after intravenous and oral administration: Importance of renal clearance and urine flow. Clin. Pharmacol. Ther.23, 329–337 (1978)
Editorial. Cimetidine for ever (and ever and ever ...)? Br. Med. J.1978/I, 1435–1436
Fortrand, J. S.: Placebos, antacids and cimetidine for duodenal ulcer. New Engl. J. Med.298, 1081–1083 (1978)
Frost, F., Rahbek, I., Rune, S. J., Jensen, K. B., Gudmar-Høyer, E., Krage, E., Rask-Madsen, J., Wulff, H. R., Garbøl, J., Jensen, K. B., Højlund, M., Nissen, V. R.: Cimetidine in patients with gastric ulcer: A multicentre controlled trial. Br. Med. J.1977/II, 795–799
Griffiths, R., Lee, R. M., Taylor, D. C.: Kinetics of cimetidine in man and experimental animals: Cimetidine: Proceedings of the second international symposium on histamine H2-receptor antagonists. pp. 38–51. Amsterdam: Excerpta Medica 1977
Kwan, K. G., Breault, G. O., Umbenhauer, E. R., McMahon, F. G., Duggan, D. E.: Kinetics of indomethacin absorption, elimination and enterohepatic circulation in man. J. Pharmacokinet. Biopharm.4, 255–280 (1976)
Lee, R. M., Osborne, P. M.: High-pressure liquid chromatographic determination of cimetidine sulphoxide in human blood and urine. J. Chromatogr.146, 354–360 (1978)
Randolph, W. C., Osborne, W. L., Walkenstein, S., Intoccia, A. P.: High-pressure liquid chromatographic analysis of cimetidine, a histamine H2-receptor antagonist, in blood and urine. J. Pharm. Sci.66, 1148–1150 (1977)
Rowland, M., Benet, L. Z., Graham, G. G.: Clearance concepts in pharmacokinetics. J. Pharmacokinet. Biopharm.1, 123–136 (1973)
Spence, R. W., Creak, D. R., Celestine, L. R.: Influence of a meal on the absorption of cimetidine — a new histamine H2-receptor antagonist. Digestion14, 127–132 (1976)
Spence, R. W., Celestin, L. R., De la Guardia, R., MacMullen, C. A., Mc Cormick, D. A.: Biliary secretion of cimetidine in man. Proceedings of the second international symposium on histamine H2-receptor antagonist. pp. 81–84. Amsterdam: Excerpta Medica 1977
Taylor, D. C., Cresswell, P. R., Bartlett, D. C.: The metabolism and elimination of cimetidine, a histamine H2-receptor antagonist, in the rat, dog and in man. Drug Metab. Dispos.6, 21–30 (1978)
Wagner, J. G.: Fundamentals of Clinical Pharmacokinetics. Hamilton, Illinois: Drug Intelligence Publications 1975
Walkenstein, S. S., Dubb, J. W., Randolph, W. C., Westlake, W. J., Stote, R. M., Intoccia, A. P.: Bioavailability of cimetidine in man. Gastroenterology74, 360–365 (1978)
References added in proof
Alván, G.: Individual differences in the disposition of drugs metabolised in the body. Clinical Pharmacokinetics3 (2), 155–175 (1978)
Bodemar, G., Norlander, B., Fransson, L., Walan, A.: The absorption 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. Br. J. Clin. Pharmacol.7, 23–31 (1979)
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Grahnén, A., von Bahr, C., Lindström, B. et al. Bioavailability and pharmacokinetics of cimetidine. Eur J Clin Pharmacol 16, 335–340 (1979). https://doi.org/10.1007/BF00605632
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DOI: https://doi.org/10.1007/BF00605632