Drug Interactions between Theophylline and H2-Antagonists, Roxatidine Acetate Hydrochloride and Cimetidine: Pharmacokinetic Analysis in Rats in vivo.

The effects of roxatidine acetate hydrochloride (Rox) on the pharmacokinetics of theophylline were compared to those of cimetidine in rats in vivo, Cimetidine or Rox was maintained at a steady state level using continuous infusion, then theophylline was injected into the rats as a bolus (7.5 mg/kg). Cimetidine showed competitive inhibition of theophylline elimination in vivo, with an inhibition constant (Ki) of 28.5 microM. Cimetidine significantly decreased the total body clearance and extended the plasma half-life of theophylline, but did not change its volume of distribution. In contrast, Rox did not significantly influence the pharmacokinetics of theophylline in rats. The in vivo animal model used in the present study for investigating the mechanism of the drug interaction showed good agreement with the results obtained in clinical and in vitro studies.