Influences of Immobilization and Footshock Stress on Pharmacokinetics of Theophylline and Caffeine in Rats

The influences of immobilization and footshock stress on pharmacokinetics of theophylline (20 mg kg^?1) and caffeine (30 mg kg^?1) administered orally were examined in rats. The immobilization stress for 30 min or 1 h immediately after oral administration caused marked immobilization period-related decreases in plasma theophylline concentrations during the absorption phase, but did not affect plasma caffeine concentrations. The k_a and C_max values for theophylline were significantly decreased, and the t_max was significantly increased. On the other hand, when the immobilization stress was loaded for 1 or 3 h before the oral administration, the plasma theophylline or caffeine concentrations were not affected. The footshock stress for 30 min immediately after oral administration did not significantly decrease plasma theophylline concentrations during the absorption phase. These results suggest that the pharmacokinetics of theophylline are influenced by strong stress, possibly due to the inhibition of its absorption from the gastrointestinal tract, but the pharmacokinetics of caffeine are not influenced by stress, probably due to its central action.