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

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Pharmacokinetics and Metabolism of Natural Methylxanthines in Animal and Man

Arnaud, Maurice J.·2011·Handbook of experimental pharmacology

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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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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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Pharmacokinetics and Metabolism of Natural Methylxanthines in Animal and Man

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