Cimetidine inhibition of theophylline elimination: The influence of adult age and the time course

The effect of placebo or cimetidine at a dose of 1 g daily on theophylline elimination was studied in a double-blind control manner in twelve healthy adult males aged 19-31 years. In a group of six, placebo had no effect on any of theophylline half-life (t1/2), volume of distribution (Vd), and total body clearance (CL). In another group of six, theophylline t1/2 rose significantly from 5.48 to 9.04 h (p less than 0.001) after 48 h and to 8.98 h (p less than 0.001) after a week pretreatment with cimetidine. Correspondingly, CL (ml min-1kg-1) fell to 0.66 (p less than 0.025) and 0.60 (p less than 0.01). Changes after 48 h pretreatment were not different from those after a week pretreatment. Seven days after the last cimetidine dose, theophylline disposition had reverted to the control level. There was no significant change in Vd. In five elderly subjects aged 56-68 years, a week of dosing with cimetidine caused a rise in t1/2 (7.17 h to 10.39 h; p less than 0.001) and a fall in CL (0.77 ml min-1kg-1 to 0.53 ml min-1kg-1; p less than 0.005) without significantly altering Vd. In two subjects, there was restoration of theophylline disposition to the control level 72 h after cessation of cimetidine intake. Changes in the elderly were not significantly different from those in the younger ones. Data indicate that cimetidine-induced impairment of theophylline disposition is of rapid onset, has rapidly attainable maximum effect, and is rapidly reversible. Furthermore elderly individuals are just as susceptible to it as the younger adults.