Summary
The effects of Cimetidine and a new, potent H2-antagonist, famotidine, on the single dose pharmacokinetics of theophylline were examined in rats. Male Sprague-Dawley rats (6 rats/group) received an i.v. dose of theophylline (6 mg/kg) alone a n d in conjunction with an i.v. dose of famotidine (10 mg/kg) or Cimetidine (10 mg/kg). Venous blood samples were collected serially for seven hours after theophylline infusion a n d analyzed for theophylline concentration by HPLC. Concomitant famotidine administration did not alter any of the pharmacokinetic parameters of theophylline (AUC0-∞; 38.1±8.7 vs. 38.8±6.3 μg.hr.ml-1), while Cimetidine demonstrated a significant reduction in theophylline systemic clearance (0.11±0.02 vs. 0.16±0.02 L/hr/kg; p<0.001), a 40% prolongation of half-life (2.8±0.9 vs. 2.0±0.5 hr), with no change in the volume of distribution (0.39±0.1 vs. 0.41±0. 1 3 L/kg). These results suggest that in contrast to Cimetidine, famotidine, a non-imidazole H2-receptor antagonist, does not interfere with theophylline disposition in the rat.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Klotz U. and Reimann I. (1980): Delayed clearance of diazepam due to Cimetidine. New Engl. J. Med.,302, 1012–1014.
Desmond P.V., Patwardhan R.V., Schenker S. and Speeg K.V. Jr. (1980): Cimetidine impairs elimination of chlorodiazepoxide (librium) in man. Ann. Intern. Med.,93, 266–268.
Puurunen J., Sotaniemi E. and Pelkonen O. (1980): Effect of Cimetidine on microsomal drug metabolism in man. Eur. J. Clin. Pharmacol.,18, 185–187.
Reitberg D.P., Bernhard H. and Schentag J.J. (1981): Alteration of theophylline clearance and half-life by Cimetidine in normal volunteers. Ann. Intern. Med.,95, 582–585.
Knodell R.G., Holtzman J.L., Cranksham D.L., Steele N.M. and Stanley L.N. (1982): Drug metabolism by rat a n d human hepatic microsomes in response to interaction with H-receptor antagonists. Gastroenterology,82, 84–88.
Klotz V. and Reimann I. (1980): Influence of Cimetidine on the pharmacokinetics of demethyldiazepam and oxazepam. Eur. J. Clin. Pharmacol.,18, 517–520.
Patwardhan R.V., Yarborough G., Desmon P.V., Johnson R.F., Schenker S. and Speeg K.V. Jr. (1980): Cimetidine spares the glucuronidatism of lorazepam and oxazepam. Gastroenterology,79, 912–916.
Henry D.A., MacDonald I.A., Kitchingman G., Bell G.D. and Langman M.J.S. (1980): Cimetidine a n d ranit i d i n e: Comparison of effects on hepatic drug metabolism. Br. Med. J.,281,115–111.
Adams F.R., Vandemark F.L. and Schmidt G.J. (1976): More sensitive high pressure liquid chromatographic determination of theophylline in serum. Clin. Chem.,22, 1903–1906.
Rocci M.L. Jr. and Jusko W.J. (1983): LAG RAN program for area a n d moments i n pharmacokinetic analysis. Computer Programs in Biomed.,16, 203–216.
Benet L.Z. and Galeazzi R.L. (1979): Non-compartmental determination of the steady-state volume of distribution. J. Pharm. Sei.,68, 1071–1074.
Shiver B.A. and Bell W.R. (1979): Cimetidine potentiation of the hypoprothrombinemic effect of warfarin. Ann. Intern. Med.,90, 348–349.
Wallin B.A., Jacknowity A. and Raich P.C. (1979): Cimetidine and effect of warfarin. Ann. Intern. Med.,90, 993.
Mojaverian P., Swanson B.N., Dudash M.L., Vlasses P.H. and Ferguson R.K. (1982): Influence of Cimetidine on the pharmacokinetics of morphine in rats. Research Communications in Substances of Abuse,3, 1–10.
Lohmann S.M. and Miech R.P. (1976): Theophylline metabolism by the rat liver microsomal system. J. Pharmacol. Exp. Ther.,196, 213–225.
Rendic S., Sunjic R., Toso R. and Kajfez F. (1979): Interaction of Cimetidine with liver microsomes. Xenobiotica,9, 555–564.
Wilkinson C.F., Metnarski K., Hicks L.J. (1973): Substituted imidazoles as inhibitors of microsomal oxidation and insecticide synergists. Pesticide Biochem. Physiol.,4, 299–312.
Mojaverian P., Fedder I.L., Vlasses P.H., Rotmensch H.H., Rocci M.L. Jr., Swanson B.N. and Ferguson R.K. (1982): Cimetidine does not alter morphine disposition in man. Br. J. Clin. Pharmac.,14, 809–813.
Grasela D.M. and Rocci M.L. Jr. (1984): Inhibition of carbamazepine metabolism by Cimetidine. Drug Metab., Disp.,12, 204–208.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mojaverian, P., Rocci, M.L., Saccar, C.L. et al. Cimetidine versus famotidine: the effect on the pharmacokinetics of theophylline in rats. European Journal of Drug Metabolism and Pharmacokinetics 10, 155–159 (1985). https://doi.org/10.1007/BF03189710
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03189710