Multiple dose pharmacokinetics of caffeine administered in chewing gum to normal healthy volunteers.
The purpose of this study was to examine the pharmacokinetics of three doses of caffeine administered as Stay Alert 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 200 mg caffeine and placebo. Subjects were 48 (n = 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 2,400, 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.


RESULTS
The mean T(max) after the third dosing ranged from 0.37 to 1.12 h. C(max) for 50, 100 and 200 mg was 2.69, 3.45 and 6.33 mg/l, respectively. AUC(inf) for 50, 100 and 200 mg group was 33.2, 46.94 and 86.94 mg/l * h, respectively. AUC(inf) values suggested a dose proportionate increase. Dose normalized C(max) and AUC(0-tau) values across doses were not significantly different, suggesting linearity was maintained after multiple doses of the Stay Alert chewing gum. There were no group related differences in elimination.


CONCLUSIONS
The results suggest that caffeine administered in the gum formulation (Stay Alert 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.
Syed
Shariq A
SA
Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, AHB 540A, 100 Penn Street, 21201, USA.
Kamimori
Gary H
GH
Kelly
William
W
Eddington
Natalie D
ND
D000042:Absorption; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002638:Chewing Gum / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009061:Mouth Mucosa / Q000378:metabolism
D000697:Central Nervous System Stimulants; D002638:Chewing Gum; D002110:Caffeine