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

Abstract

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 (t_1/2), volume of distribution (V_d), and total body clearance (CL). In another group of six, theophylline t_1/2 rose significantly from 5.48 to 9.04 h (p < 0.001) after 48 h and to 8.98 h (p < 0.001) after a week pretreatment with cimetidine. Correspondingly, CL (ml min⁻¹kg⁻¹) fell to 0.66 (p < 0.025) and 0.60 (p < 0.01). Changes after 48h 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 V_d. In five elderly subjects aged 56–68 years, a week of dosing with cimetidine caused a rise in t_1/2 (7.17 h to 10.39 h; p < 0.001) and a fall in CL (0.77 ml min⁻¹kg⁻¹ to 0.53 ml min⁻¹kg⁻¹; p < 0.005) without significantly altering V_d. 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.