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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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Influence of alcohol and caffeine consumption on caffeine elimination
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“After oral administration, it is rapidly and completely absorbed (Axelrod & Reichenthal 1953; Bonati et al. 1982; Marks 1973).”
BackgroundThe effects of 600 mg of slow release caffeine on mood and alertness.
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“This cycle has never been described at rest and the bioavailability of caffeine after oral intake was found to be 1 [2].”
BackgroundCardiovascular Effects of Coffee: Is It a Risk Factor?
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“23 29 Caffeine is metabolized primarily in the liver through the cytochrome P450 system.”
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“…principal initial step is 3- demethylation of caffeine (1,3,7-trimethylxanthine) to paraxanthine (1,7-dimethylxanthine); 72e80% of ingested caffeine follows this route, and paraxanthine plasma levels exceed those of caffeine within 8e10 h of ingestion (Bonati et al., 1982; Tang-Liu et al., 1983).”
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“Caffeine (1, 3, 7-trimethylxanthine) belongs to the purines and its main effect is as a psychostimulant in the CNS.”
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“Previous research has shown that the optimum time for complete caffeine absorption is between 15 and 120 min post ingestion (Blanchard and Sawers, 1983; Bonati et al., 1982; Kamimori et al., 1995, 2000) therefore researchers have often tested performance 1 h post ingestion (Ryan et al.”
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“Given that the half life of caffeine is 4–6 h((15)), it is conceivable that it could have metabolic actions well beyond those of a first meal.”
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“5 h (Arnaud 1987; Bonati et al. 1982).”
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Self-citationDose-dependent model of caffeine effects on human vigilance during total sleep deprivation
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“The pharmacokinetics (PK) of caffeine and its dose-dependent metabolism in humans have been well characterized (Bonati et al., 1982; Denaro et al., 1990), and its mechanism of action (antagonism of adenosine receptors) is also well-understood (Bertorelli et al.”
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The Physiological Effects of Coffee Consumption
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The Effect of Coffee and Caffeine Consumption on Patients with Multiple Sclerosis-Related Fatigue
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“Due to its hydrophobic structure, caffeine can pass the blood-brain barrier and thus also act on receptors in the brain [16,18].”
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“The absorption from the human gastrointestinal tract is rapid, reaching 99% about 45min after consumption (Bonati et al. 1982).”
BackgroundOLFACTORY DECREMENTS AS A FUNCTION OF TWO NIGHTS OF SLEEP DEPRIVATION
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“The half-life of orally administered caffeine has been reported to be between 3 and 5 h (Bonati et al. 1982; Kamimori et al. 1995).”
BackgroundPark, G. J., Wiseman, E., George, J., Katelaris, P., Seow, F. C., Fung, C. L.-S., & Ngu, M. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2011.06760.x · Cited by 28
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Risks associated with fat burners: A toxicological perspective
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“Mean age of onset in years (range) 62 (44-86) Mean age at diagnosis (range) 66 (54-87) Females (%) 32 (80%) Quality (a) Sharp 26 (65%) (b) Dull 14 (c) Burning 2 (d) Throbbing 9 (e) Bilateral 24 (60%) Intensity (a) Severe (8-10 VRS) 23 (57%) (b) Moderate (5-7 VRS) 15 (c) Mild (1-4 VRS) 2 Unilateral 16 (40%) Time of ons…”
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Caffeine induces cardiac and other malformations in the rat
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Caffeine Timing Improves Lower-Body Muscular Performance: A Randomized Trial
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“Following ingestion, caffeine is completely absorbed in the stomach and small intestine, with plasma caffeine concentration increasing in a dose-dependent manner (33, 34).”
BackgroundInfluentialExercise and caffeine improve sustained attention following fatigue independent of fitness status
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“for caffeine absorption [36,37], participants waited 20 min following treatment ingestion prior to completing the initial CPT.”
MethodCaffeine metabolism in patients with chronic liver disease
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“Previous studies in man have shown that caffeine elimination follows first order kinetics after this oral dose, which is maintained beyond several half lives.6 Caffeine clearance was calculated as Cl=kelXVd, using a constant volume ofdistribu-tion of 0-61/kg body weight.”
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“Some of the factors that were not included in the model of t1⁄2, as they are unlikely to affect t1⁄2, include body mass index [39], sex [5], habitual use of caffeine [6,8,12], dose of caffeine ingested [40], and menstrual phase [33] (n.”
BackgroundNabbi-Schroeter, D., Elmenhorst, D., Oskamp, A., Laskowski, S., Bauer, A., & Kroll, T. (2017) · Molecular Imaging and Biology · doi:10.1007/s11307-017-1116-4 · Cited by 24
“Estimation of the residual plasma levels were performed [32] considering the dose-dependent half-life t1⁄2 of caffeine (1–4 h) [32–35] and the decaffeinated period (4–6 h).”
BackgroundMethodThe bronchodilator effect of caffeine in adult asthmatics.
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The complexity of coffee and its impact on metabolism
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“The pharmacokinetics (PK) of caffeine and its dose-dependent metabolism in humans have been well characterized (Bonati et al., 1982; Denaro et al., 1990) and the mechanism of action (antagonism of adenosine receptors) is also well-understood (Bertorelli et al.”
BackgroundReal and Perceived Effects of Caffeine on Sprint Cycling in Experienced Cyclists.
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Parkinson's disease and CYP1A2 activity
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Caffeine, Is it effective for prevention of postdural puncture headache in young adult patients?
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“The dose of caffeine used in our study (500 mg) contains 250 mg of caffeine plus 250 mg of sodium benzoate to enhance solubility before parenteral use, but in the study by Sechzer [20] oral caffeine (300 mg of anhydrous powder) the dose was 120% greater than the dose used in our study, caffeine is almost completely ab…”
MethodRhabdomyolysis induced by excessive coffee drinking
Chiang, W., Liao, M.-T., Cheng, C.-J., & Lin, S.-H. (2013) · Human & Experimental Toxicology · doi:10.1177/0960327113510536 · Cited by 22
“It is a natural alkaloid methylxanthine that is metabolized in the liver by polymorphic cytochrome P450 into paraxanthine, theobromine, and theophylline.(10,11) These metabolites together with caffeine competitively bind to the adenosine receptor to increase catecholamine release.”
BackgroundI. Kinetics and metabolism of theobromine in male rats
Bonati, M. R., Latini, R., Sadurska, B., Riva, E., Galletti, F., Borzelleca, J. F., Tarka, S. M., Arnaud, M. J., & Garattini, S. K. (1984) · Toxicology · doi:10.1016/0300-483x(84)90143-4 · Cited by 21
Self-citationDevelopment and initial validation of a caffeine craving questionnaire
West, O., & Roderique‐Davies, G. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107082746 · Cited by 21
“…pharmacokinetics; 1–15 min, no effect (Arnaud, 1993; Sawynok and Yaksh, 1993) (n 11); 16–120 min, time to reach significant brain concentrations (Bonati et al., 1982; Arnaud, 1993; Sawynok and Yaksh, 1993; Mckim, 2003) (n 48); 180–420 min (3–7 h), half-life (Bonati et al., 1985; Magkos and…”
BackgroundEffects of altitude (4300 M) on the pharmacokinetics of caffeine and cardio-green in humans
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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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