Effects of cimetidine on caffeine disposition in smokers and nonsmokers

Abstract

The absorption, distribution and elimination of caffeine, 2 mg/kg by mouth, were evaluated in 6 smokers and 6 nonsmokers before and on the 4th day of administration of cimetidine [used to treat many gastrointestinal disorders], 300 mg by mouth every 6 h. Caffeine absorption, assessed by the maximal serum caffeine concentration (Cmax) and the time to reach Cmax (tmax), was very rapid relative to elimination. The total body clearance (TBC) of caffeine was higher (2.49 .+-. 0.35 and 1.59 .+-. 0.19 ml/kg per min, P < 0.05) and the elimination half-life (t1/2) shorter (190 .+-. 15 and 276 .+-. 30 min, P < 0.05) in smokers than nonsmokers; however, Cmax, tmax and the apparent volume of distribution (Vd,app) did not differ (P > 0.05). Cimetidine decreased the TBC of caffeine by 31% (to 1.73 .+-. 0.28 ml/kg per min, P < 0.05) and by 42% (to 0.92 .+-. 0.11 ml/kg per min, P < 0.01) in smokers and nonsmokers. The increases in t1/2 were 45% (to 276 .+-. 25 min, P < 0.05) and 96% (to 542 .+-. 123 min, P < 0.05). Cmax, tmax and Vd,app were evidently unaffected by cimetidine. Caffeine induced similar slight increases in blood pressure and pulse rate in smokers and nonsmokers both before and during cimetidine dosing.