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Cited by 390Coffee research and impactsDrug Solubulity and Delivery SystemsPharmacogenetics and Drug Metabolism

The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers

Kamimori, Gary H, Karyekar, Chetan S, Otterstetter, Ronald, Cox, Donna S, Balkin, Thomas J, Belenky, Gregory L, Eddington, Natalie D·2002·International Journal of Pharmaceutics
DOI 10.1016/s0378-5173(01)00958-9
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Abstract

Objective The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation. Methods This was a double blind, parallel, randomized, seven treatment study. The treatment groups were: 50, 100, and 200 mg gum, 50, 100, and 200 mg capsule, and a placebo. Subjects consisted of 84 (n=12 per group); healthy, non-smoking, males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were randomly assigned to the treatment groups. Blood samples were collected pre-dose and at 5, 15, 25, 35, 45, 55, 65, 90 min and 2, 3, 4, 6, 8, 12, 16 and 29 h post administration. Plasma caffeine levels were analyzed by a validated UV-HPLC method. Results Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0-120.0 min for the capsule groups. The Tmax, for the pooled data was significantly lower (P<0.05) for the gum groups as compared with the capsule groups. Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum (P<0.05). The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1. Relative bioavailability of the gum formulation after the 50, 100 and 200 mg dose was 64, 74 and 77%, respectively. When normalized to the total drug released from the gum (85%), the relative bioavailability of the 50, 100 and 200 mg dose were 75, 87, and 90%, respectively. No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose. Within each dose level, there were no significant formulation related differences in Cmax. No significant differences were observed in the elimination of caffeine after the gum or capsule. Conclusions The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa. In addition, for the 100 and 200 mg groups, the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation. These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation, which is advantageous in situations where the rapid reversal of alertness and performance deficits resulting from sleep loss is desirable.

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Crossref · 10.1016/s0378-5173(01)00958-9

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Research works printed but not linked: 1

  1. Reyner, 1998, Caffeine (200 mg) as a countermeasure to early morning driver sleepiness after nil or restricted sleep, J. Sleep Res., 7, 223

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Authors
Kamimori, G. H., Karyekar, C. S., Otterstetter, R., Cox, D. S., Balkin, T. J., Belenky, G. L., & Eddington, N. D.
Affiliations
  • Walter Reed Army Institute of Research (US)
  • University of Maryland, Baltimore (US)
Corresponding author
Eddington, Natalie D
ORCID
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2002-03
Volume
234
Issue
1-2
Pages
159-167
ISSN
0378-5173 (ISSN-L)
DOI
10.1016/s0378-5173(01)00958-9
OpenAlex
W2077985682
Semantic Scholar
c5f1c237242466a88e716b09ee8b1bc4ee0427a0
Cited by
390
References
16
Citations by year
2026: 18 · 2025: 23 · 2024: 31 · 2023: 25 · 2022: 22 · 2021: 31 · 2020: 49 · 2019: 18 · 2018: 20 · 2017: 18 · 2016: 17 · 2015: 13 · 2014: 17 · 2013: 10 · 2012: 15
FWCI
3.35
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • International Journal of Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
caffeine, chewing gum, capsule formulation, relative bioavailability, pharmacokinetics, Tmax, absorption rate constant, drug delivery route comparison, healthy volunteers, dose proportionality, elimination half-life, interindividual variability, caffeine metabolism
MeSH terms
Adolescent, Adult, Central Nervous System Stimulants, Biological Availability, Caffeine, Capsules, Chewing Gum, Chromatography, High Pressure Liquid, Double-Blind Method, Humans, Intestinal Absorption, Male, Spectrophotometry, Ultraviolet, Area Under Curve

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