Multiple Dose Pharmacokinetics of Caffeine Administered in Chewing Gum to Normal Healthy Volunteers

Abstract

The purpose of this study was to examine the pharmacokinetics of three doses of caffeine administered as Stay Alert1 chewing gum in a multiple dose regimen. Methods: A double-blind, parallel randomized, four-treatment study design was employed. The treatment groups were: 50, 100 and 200mg caffeine and placebo. Subjects were 48 (n ¼ 12 per group), healthy, non-smoking, males and females who had abstained from caffeine ingestion for at least 20 h prior to dosing, who were randomly assigned to the treatment groups. Caffeine was administered at 2400, 0200 and 0400 h depending on the treatment group. Blood samples were collected pre-dose and at 5, 15, 30, 45, 60, 75, 90 and 105 min after each caffeine dose. Samples were also collected at 7.5, 8.5 and 18 h after the last dose of caffeine. Plasma caffeine levels were analysed by a validated UV-HPLC method. Result: The mean Tmax after the third dosing ranged from 0.37 to 1.12 h. Cmax for 50, 100 and 200mg was 2.69, 3.45 and 6.33 mg/l, respectively. AUCinf for 50, 100 and 200mg group was 33.2, 46.94 and 86:94 mg=l h, respectively. AUCinf values suggested a dose proportionate increase. Dose normalized Cmax and AUC0 t values across doses were not significantly different, suggesting linearity was maintained after multiple doses of the Stay Alert1 chewing gum. There were no group related differences in elimination. Conclusions: The results suggest that caffeine administered in the gum formulation (Stay Alert1 chewing gum) via a multiple dosing regimen provides an effective and convenient means of maintaining effective concentrations of caffeine that would in some operational scenarios be desirable for maintaining alertness and performance in sleep deprived individuals. Copyright # 2005 John Wiley & Sons, Ltd. Key words: caffeine chewing gum; caffeine multiple dose; pharmacokinetics; buccal absorption