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Cited by 259Coffee research and impactsPharmacogenetics and Drug MetabolismAlcohol Consumption and Health Effects

The DOI matches its Crossref record; 311 of the 311 references it cites were found in a registry or an index.

Pharmacokinetics and Metabolism of Natural Methylxanthines in Animal and Man

Arnaud, Maurice J.·2011·Handbook of experimental pharmacology
DOI 10.1007/978-3-642-13443-2_3
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Abstract

Caffeine, theophylline, theobromine, and paraxanthine administered to animals and humans distribute in all body fluids and cross all biological membranes. They do not accumulate in organs or tissues and are extensively metabolized by the liver, with less than 2% of caffeine administered excreted unchanged in human urine. Dose-independent and dose-dependent pharmacokinetics of caffeine and other dimethylxanthines may be observed and explained by saturation of metabolic pathways and impaired elimination due to the immaturity of hepatic enzyme and liver diseases. While gender and menstrual cycle have little effect on their elimination, decreased clearance is seen in women using oral contraceptives and during pregnancy. Obesity, physical exercise, diseases, and particularly smoking and the interactions of drugs affect their elimination owing to either stimulation or inhibition of CYP1A2. Their metabolic pathways exhibit important quantitative and qualitative differences in animal species and man. Chronic ingestion or restriction of caffeine intake in man has a small effect on their disposition, but dietary constituents, including broccoli and herbal tea, as well as alcohol were shown to modify their plasma pharmacokinetics. Using molar ratios of metabolites in plasma and/or urine, phenotyping of various enzyme activities, such as cytochrome monooxygenases, N-acetylation, 8-hydroxylation, and xanthine oxidase, has become a valuable tool to identify polymorphisms and to understand individual variations and potential associations with health risks in epidemiological surveys.

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Crossref · 10.1007/978-3-642-13443-2_3

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Citations

Cites

Research works printed but not linked: 16

  1. Arnaud MJ (1980) Metabolism of labeled paraxanthine in the rat: comparison of rat and human metabolic pathway. Nutr Rev 38(5):196–200
  2. Arnaud MJ (1983) The effect of dietary factors on the bioavailability of methylxanthines. Proceedings of the toxicology forum, Aspen, Colorado, pp 234–243
  3. Arnaud MJ (1988) The metabolism of coffee constituents in coffee, vol 3. In: Clarke RJ, Macrae R (eds) Physiology. Elsevier, London, pp 33–55
  4. Arnaud MJ (1998) Pharmacokinetics and metabolism of caffeine. In: Snel J, Lorist MM (eds) Nicotine, caffeine and social drink, behaviour and brain function. Harwood, Amsterdam, pp 153–165
  5. Arnaud MJ, Bracco I (1981) Distribution and metabolism of theophylline in the pregnant rat: presence of a blood brain barrier. Experientia 37(6):665
  6. Arnaud MJ, Enslen M (1992) The role of paraxanthine in mediating physiological effects of caffeine. In: 14th international conference in coffee science, San Francisco, 14–19 July 1991. Proceedings ASIC, Paris, pp 71–79
  7. Arnaud MJ, Gétaz F (1982) Postnatal establishment of a blood-brain barrier for theobromine in the rat. Experientia 38(6):752
  8. Arnaud MJ, Gétaz F (1983) Theobromine distribution in the pregnant rat and the fetus and the impairment of its metabolism due to pregnancy. Experientia 39(6):678
  9. Arnaud MJ, Richli U, Philippossian G (1986b) Isolation and identification of paraxanthine glucuronide as the major caffeine metabolite in mice. Experientia 42(6):696
  10. Arnaud MJ, Welsch C (1979b) Metabolism of [1-Me-14C] paraxanthine in the rat: identification of a new metabolite. Experientia 35(7):946
  11. Arnaud MJ, Welsch C (1980a) Caffeine metabolism in human subjects. In: Proceedings of the ninth international colloquium on science and technology of coffee. Association Scientifique Internationale du Cafe, London, pp 385–395
  12. Arnaud MJ, Welsch C (1980b) Quantitative analysis of theophylline metabolites by HPLC, after oral or i.v. administration. Experientia 36(6):704
  13. Arnaud MJ, Wietholtz H, Voegelin M, Bircher J, Preisig R (1982b) Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test. In: Sato R (ed) Microsomes drug oxidation and drug toxicity. Wiley, New York, pp 443–444
  14. Levy M, Granit L, Zylber-Katz E (1984) Chronopharmacokinetics of caffeine in healthy volunteers. Annu Rev Chronopharmacol 1:97–100
  15. Morisot C, Simoens C, Trublin F, Lhermitte M, Gremillet C, Robert MH, Lequin P (1990) Efficacité de la caffeine transcutanée dans le traitement des apnées du prématuré. Arch Fr Pediatr 47(3):221–224
  16. Schrenk D (1998) Impact of dioxin-type induction of drug-metabolizing enzymes on the metabolism of endo- and xenobiotics. Biochem Pharmacol 5(8):1155–1162

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Metadata

Authors
Arnaud, M. J.
Corresponding author
Arnaud, Maurice J.
ORCID
Arnaud, Maurice J.
Venue
Handbook of experimental pharmacology
Publisher
Springer Berlin Heidelberg
Published
2010-08-19
Issue
200
Pages
33-91
ISSN
  • 0171-2004 (ISSN-L)
  • 1865-0325
DOI
10.1007/978-3-642-13443-2_3
OpenAlex
W135619738
Cited by
259
References
310
Citations by year
2026: 10 · 2025: 20 · 2024: 26 · 2023: 24 · 2022: 18 · 2021: 21 · 2020: 26 · 2019: 20 · 2018: 13 · 2017: 16 · 2016: 9 · 2015: 12 · 2014: 13 · 2013: 8 · 2012: 13
FWCI
39.30
Type
book chapter
Language
en
Open access
closed
Locations
  • Handbook of experimental pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
methylxanthines, caffeine, theophylline, theobromine, paraxanthine, pharmacokinetics, drug metabolism, hepatic metabolism, CYP1A2, enzyme polymorphism, oral contraceptives, pregnancy, smoking, obesity, diet effects, alcohol, xanthine oxidase, N-acetylation, cytochrome P450, species differences, drug interactions
MeSH terms
Animals, Caffeine, Female, Humans, Male, Theobromine, Theophylline, Tissue Distribution, Xanthines, Metabolic Networks and Pathways

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