title: 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 six smokers and six nonsmokers before and on the fourth day of administration of cimetidine, 300 mg by mouth every 6 hr. Caffeine absorption, assessed by the maximal serum caffeine concentration (C max) and the time to reach Cmax (t max), 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/min, P less than 0.05) and the elimination half-life (t1/2) shorter (190 +/- 15 and 276 +/- 30 min, P less than 0.05) in smokers than nonsmokers, but Cmax, tmax, and the apparent volume of distribution (Vd, app) did not differ (P greater than 0.05). Cimetidine decreased the TBC of caffeine by 31% (to 1.73 +/- 0.28 ml/kg/min, P less than 0.05) and by 42% (to 0.92 +/- 0.11 ml/kg/min, P less than 0.01) in smokers and nonsmokers. The increases in t1/2 were 45% (to 276 +/- 25 min, P less than 0.05) and 96% (to 542 +/- 123 min, P less than 0.05). Cmax, tmax, and Vd, app were unaffected by cimetidine. Caffeine induced similar slight increases in blood pressure and pulse rate in smokers and nonsmokers both before and during cimetidine dosing.
mesh_terms: D000328:Adult; D002110:Caffeine / Q000097:blood / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012907:Smoking; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D006146:Guanidines; D002110:Caffeine; D002927:Cimetidine