Theophylline-ranitidine drug interaction in the beagle dog

Ranitidine (300 mg p.o.) and theophylline (15 mg/kg i.v.) were studied in Beagle dogs for possible drug interaction. Using a crossover design drugs were given alone and in combination. For the combination treatment ranitidine was given twice daily for two days before theophylline was administered. No significant differences in drug disposition were found for theophylline and ranitidine when given simultaneously. The mean total clearance of theophylline decreased in the presence of ranitidine by about 10%, and the mean total clearance of ranitidine decreased in the presence of theophylline by about 17%. Due to the small number of subjects, not more than a possible trend for reduction in total clearance was found. The total clearance in ml/min/kg for both ranitidine and theophylline is about 3 times higher in the Beagle dog than in man.