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.

1,3,7-Trimethylxanthine (Caffeine) May Exacerbate Acute Inflammatory Liver Injury by Weakening the Physiological Immunosuppressive Mechanism

“…It is also interesting that caffeine is detected in habitual caffeine-consuming humans at concentrations capable of antagonizing A2AR, 10 -50 M in moderate to heavy caffeine consumers (43,44). Other studies showed that when humans acutely ingested 2-2.5 mg/kg caffeine (corresponding to the amount in two cups of coffee), blood caffeine concentration was ϳ20 M (41,45,46). In contrast, amounts of caffeine much higher than what people usually consume will be required for the immunosuppressive effects of caffeine.…”

“…Therefore, the same per kilogram dose of caffeine does not reproduce the same blood concentration in humans and mice. Indeed, the serum caffeine concentration after a dose of 2 mg/kg was 10 M in mice while it was 25 M in humans (41,42). Considering such differences, it is suggested that 10 mg/kg of caffeine in rodents represents 3.5 mg/kg in humans, which corresponds to 2-3 cups of coffee for a 70-kg human (1).…”

Transdermal Nicotine Maintenance Attenuates the Subjective and Reinforcing Effects of Intravenous Nicotine, but not Cocaine or Caffeine, in Cigarette-Smoking Stimulant Abusers

“…Although previous studies have shown that caffeine can enhance the reinforcing effects of nicotine (Shoaib et al, 1999;Jones and Griffiths, 2003), no study has evaluated whether nicotine enhances the reinforcing effects of caffeine. However, it is known that cigarette smoking decreases the half-life of caffeine by as much as 50% (Parsons and Neims, 1978;May et al, 1982). Thus, higher rates of caffeine consumption among cigarette smokers may be due to the faster rate of caffeine elimination.…”

The Effect of Erythromycin on the Disposition Kinetics of Warfarin

“…Interestingly, the inhibitory effect of erythromycin is greatest in subjects who clear warfarin relatively slowly. May et al [13] reported a similar inverse relationship for cimetidine's inhibitory effect on caffeine elimination, noting that the greatest impair ment of caffeine elimination by cimetidine occurs in individuals whose elimination is initially slow.…”