Caffeine disposition in obesity.

Caffeine pharmacokinetics were studied in 16 obese (mean +/- s.e. mean body weight; 110 +/- 8 kg; % ideal body weight (IBW); 186 +/- 14%) and 23 normal body weight (64 +/- 3 kg; 103 +/- 3% IBW) subjects. Eight obese and four control subjects were cigarette smokers. After abstaining from caffeine for 48 h and an overnight fast, each subject ingested 162 mg caffeine orally. Concentrations of caffeine were measured in plasma samples obtained during the 24 h following the dose and pharmacokinetic variables were determined. The apparent volume of distribution was increased markedly in obese subjects (69.9 +/- 5.9 vs 43.6 +/- 2.8 l; P less than 0.001) in the absence of any change in oral clearance (135 +/- 14-obese vs 112 +/- 12 ml/min; NS), resulting in a trend toward increased elimination half-life (7.05 +/- 1.08-obese vs 5.40 +/- 0.40 h; NS). Apparent volume of distribution correlated well with percent IBW (r = 0.65; P less than 0.001). Caffeine clearance, suggested as a measure of in vivo cytochrome P-448 activity in humans, was not altered in obesity. In contrast, the extent of caffeine distribution increased in direct relation to body weight. If caffeine is used therapeutically, the loading dose should be calculated as a function of total body weight. Since clearance of caffeine is not related to body weight, these data indicate that a chronic dosing regimen to maintain a given plasma caffeine concentration should not be altered due to obesity.