Cimetidine versus famotidine: the effect on the pharmacokinetics of theophylline in rats

Abstract

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. © 1985 Springer-Verlag.