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Caffeine disposition after oral doses
Abstract
Caffeine (TMX) disposition was studied in mean after 1, 5, and 10 mg/kg in water, as mocha coffee (1.54 mg/kg) and as a soft drink (0.22 mg/kg). TMX and its metabolites were analyzed in plasma and urine by high-pressure liquid chromatography. The design permitted confirmation of most of the partial results in various experimental settings and contributed new data on the metabolic disposition of TMX, with specific reference to main dimethylxanthine metabolite found in plasma, paraxanthine (1,7-dimethylxanthine). Different analysis methods were compared for the calculated parameters (absorption and elimination rate constants and renal clearance)to assess the consistency of results. The kinetics of TMX and of its dimethylated metabolites in plasma were described with a model that used an analogdigital hybrid computing system. In addition to providing a comprehensive profile of TMS disposition in the healthy adult, the results indicate tha TMX exhibits dose-independent kinetics at the levels at which man normally takes TMX.
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“The kinetics of caffeine have been reported to be linear in doses up to 10 mg/kg bw (Bonati et al., 1982), whereas a later study claimed non-linearity beginning at doses as high as 500 mg, corresponding to about 7.1 mg/kg bw (Kaplan et al., 1997).”
From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Bonati et al., 1982
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Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624
Nehlig, A., Daval, J., & Debry, G. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90012-b · Cited by 1,463
Heckman, M. A., Weil, J., & de Mejía, E. G. (2010) · Journal of Food Science · doi:10.1111/j.1750-3841.2010.01561.x · Cited by 1,116
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption
Nehlig, A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014407 · Cited by 632
“In healthy humans, caffeine is apparently eliminated via first-order kinetics in a one-compartment open model system for intakes ranging from 2 to 10 mg/kg (Bonati et al., 1982; Blanchard and Sawers, 1983a).”
BackgroundButler, M. A., Iwasaki, M., Guengerich, F. P., & Kadlubar, F. F. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.7696 · Cited by 638
Metadata
- Authors
- Bonati, M., Latini, R., Galletti, F., Young, J. F., Tognoni, G., & Garattini, S.
- Affiliations
- National Center for Toxicological Research (US)
- Corresponding author
- Bonati, Maurizio
- Venue
- Clinical Pharmacology and Therapeutics
- Publisher
- Wiley
- Published
- 1982-07
- Volume
- 32
- Issue
- 1
- Pages
- 98-106
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2047855828
- Cited by
- 353
- References
- 0
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 13 · 2017: 14 · 2016: 11 · 2015: 13 · 2014: 12 · 2013: 10 · 2012: 20
- FWCI
- 8.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Plant-based Medicinal Research
- Keywords
- caffeine, oral administration, caffeine metabolites, paraxanthine, 1,7-dimethylxanthine, dimethylxanthines, absorption rate constant, elimination rate constant, renal clearance, plasma kinetics, coffee, soft drinks, pharmacokinetic modeling
- MeSH terms
- Administration, Oral, Adult, Biotransformation, Caffeine, Carbonated Beverages, Coffee, Humans, Kinetics, Male
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