Abstract
25 patients with different degrees of chronic stable renal failure received oral treatment with cimetidine over 6 days and a final dose in the morning of day 7. The doses of cimetidine were reduced according to the degree of renal failure. Plasma concentrations of cimetidine were determined before the morning dose on days 2, 3, 6 and before the final morning dose and during the day on day 7. 24-hour excretions of cimetidine were measured during the study and on day 7, 6 to 9 hours after the final morning dose.
There were significant linear relationships between the values of creatinine clearance and plasma elimination rale constant of cimetidine (p < 0.0025) and between the values of creatinine clearance and renal clearance of cimetidine (p < 0.05). On the basis of the morning plasma concentrations before and the plasma concentration curve after the final morning dose on day 7 the following dose recommendations according to pretrial values of creatinine clearance are recommended for cimetidine treatment in renal failure: 5 to 15ml/min 200mg 2 or 3 times daily, 15 to 30ml/min 200mg 3 times daily and 30 to 75ml/min 200mg 4 times daily.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bjornsson, T.D.: Use of serum creatinine concentrations to determine renal function. Clinical Pharmacokinetics 4: 200–222 (1979).
Bodemar, G.; Norlander, B.; Fransson, L. and Walan, A.: The absorption of cimetidine before and during maintenance treatment with cimetidine and the influence of a meal on the absorption of cimetidine in patients with peptic ulcer disease. British Journal of Clinical Pharmacology 7: 23–31 (1979).
Bodemar, G.; Norlander, B. and Walan, A.: Pharmacokinetics of cimetidine after single doses and during continuous treatment. Clinical Pharmacokinetics 6: 306–315 (1981).
Burland, W.L.; Duncan, W.A.M.; Hesselbo, T.; Mills, J.G.; Sharpe, P.C.; Haggie, S.J. and Wyllie, J.H.: Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man. British Journal of Clinical Pharmacology 2: 481–486 (1975).
Canavan, J.S.F. and Briggs, J.D.: Cimetidine clearance in renal failure; in Burland and Simkins (Eds) Cimetidine, pp.75–80 (Excerpta Medica, Amsterdam, Oxford 1977).
Delaney, J.C. and Ravey, M.: Cimetidine and mental confusion. Lancet 2; 512 (1977).
Friedman, S.A.; Raizner, A.E.; Rosen, H.; Solomon, N.A. and Sy, W.: Functional defects in the aging kidney. Annals of Internal Medicine 76: 41–45 (1972).
Grave, W.; Nadorp, J.H.S.M. and Rutten, J.J.M.H.: Cimetidine and renal failure. Lancet 2: 719–720 (1977).
Griffiths, R.; Lee, R.M. and Taylor, D.C.: Kinetics of cimetidine in man and experimental animals; in Burland and Simkins (Eds) Cimetidine, pp.38–51 (Excerpta Medica, Amsterdam, Oxford 1977).
Kampman, J.; Siersback-Nielsen, K.; Kristensen, M. and Molholm Hansen, J.: Rapid evaluation of creatinine clearance. Acta Medica Scandinavica 196: 517–520 (1974).
Krichman, K.H.; Cutler, R.E. and Blair, A.D.: Pharmacokinetics of cimetidine in normal and uremic humans. Clinical Research 27: 73A (1979).
Larsson, R.; Bodemar, G. and Norlander, B.: Oral absorption of cimetidine and its clearance in patients with renal failure. European Journal of Clinical Pharmacology 15: 153–157 (1979).
Larsson, R.; Bodemar, G.; Kågedal, B. and Walan, A.: The effects of cimetidine (Tagamet ®) on renal function in patients with renal failure. Acta Medica Scandinavica. 208: 27–31 (1980).
Ma, K.W.; Brown, D.C.; Master, D.S. and Silvis, S.E.: Effects of renal failure on blood levels of cimetidine. Gastroenterology 74: 473–477 (1978).
McMillen, M.A.; Ambis, D. and Siegel, J.H.: Cimetidine and mental confusion. New England Journal of Medicine 298: 284–285 (1978).
Menzies-Gow, N.: Cimetidine and mental confusion. Lancet 2: 928 (1977).
Quap, C.W.: Confusion: An adverse reaction to cimetidine therapy. Drug Intelligence and Clinical Pharmacy 12: 21 (1978).
Redolfi, A.; Borgogelli, E. and Lodola, E.: Blood level of cimetidine in relation to age. European Journal of Clinical Pharmacology 15: 257–261 (1979).
Robinson, T.J. and Mulligan, T.O.: Cimetidine and mental confusion. Lancet 2: 719 (1977).
Schentag, J.J.; Cerra, F.B.; Calleri, G.; De Glopper, E.; Rose, J.Q. and Bernard, H.: Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion. Lancet 1: 177–181 (1979).
Spears, J.B.: Cimetidine and mental confusion. American Journal of Hospital Pharmacy 35: 1035 (1978).
Vickery, T.R.: Cimetidine reaction: Drug Intelligence and Clinical Pharmacy 12: 242 (1978).
Wagner, J.G.: The kidney and urinary excretion; in Wagner (Ed) Biopharmaceutics and Relevant Pharmacokinetics, pp. 247–251 (Drug Intelligence Publications, Hamilton, Ill. 1971).
Walkenstein, S.S.; Dubb, J.W.; Randolph, W.C.; Westlake, W.J.; Stoote, R.M. and Intoccia, A.P.: Bioavailability of cimetidine in man. Gastroenterology 74: 360–365 (1978).
Wood, C.A.; Isaacson, M.L. and Hibbs, M.S.: Cimetidine and mental confusion. Journal of the American Medical Association 239: 2550–2551 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Larsson, R., Norlander, B., Bodemar, G. et al. Steady-state Kinetics and Dosage Requirements of Cimetidine in Renal Failure. Clin Pharmacokinet 6, 316–325 (1981). https://doi.org/10.2165/00003088-198106040-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-198106040-00006