Decreased systemic clearance of caffeine due to cimetidine

1 Five normal subjects received pre-treatment with cimetidine 200 mg three times daily and 400 mg at night for 6 days, or matching placebo. 2 Caffeine (300 mg) was given orally before any treatment and at the beginning of the last day of each treatment course. Treatments were randomly allocated and separated by at least one week. 3 A significant reduction occurred in the systemic clearance of caffeine and the half-life was prolonged as determined from measurement of caffeine in plasma and saliva. No change occurred in the apparent volume of distribution. 4 The oral bioavailability of caffeine was found to be complete in the one subject studied. 5 It is suggested that cimetidine inhibits the microsomal metabolism of caffeine. Although the steady state plasma caffeine would increase by approximately 70%, it is unlikely that this would produce adverse clinical effects.