Effects of equimolar doses of cimetidine and ranitidine on theophylline elimination

The disposition of theophylline was studied on four occasions in eight healthy adult males. The control mean theophylline half-life and clearance were 7.32 h and 0.86 ml min-1 kg-1, respectively. After 5 days pretreatment with placebo the corresponding values of 7.01 and 0.88 were not significantly different, as were those of 7.43 and 0.85 after 5 days pretreatment with ranitidine (1.2 g daily). Five days pretreatment with cimetidine (1.0 g daily) resulted in a significant 44.4 per cent rise in the mean theophylline half-life and a 36.1 per cent fall in clearance. The fall in clearance correlated positively (r = 0.9407) with the initial value. The volume of distribution did not change significantly throughout the study period. The fact that, at as large a dose as 1.2 g daily, ranitidine did not impair theophylline metabolism suggests that similar results reported earlier with therapeutic doses of 300 mg daily cannot be ascribed to the lower dose of ranitidine employed. It is also suggested that the risk of theophylline toxicity consequent on cimetidine coadministration will be more likely in individuals with initial high theophylline clearance.