Products of Metabolism of Caffeine

Arnaud, Maurice J.

doi:10.1007/978-3-642-69823-1_1

Cited by 38 publications

(13 citation statements)

References 108 publications

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“…There are many examples of xenobiotics with relatively simple chemical structures which undergo a remarkably complex series of metabolic conversions. Examples of such compounds include the most widely used drug in the world, caffeine (Arnaud, 1984), and the potent experimental carcinogen 2-aminofluorene (Miller, 1978). The latter compound in fact requires metabolic activation for its carcinogenic potential to be manifested.…”

Section: Drug Biotransformation Reactionsmentioning

confidence: 99%

Detoxification pathways in the liver

Grant

1991

J of Inher Metab Disea

143

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The liver plays an important rôle in protecting the organism from potentially toxic chemical insults through its capacity to convert lipophiles into more water-soluble metabolites which can be efficiently eliminated from the body via the urine. This protective ability of the liver stems from the expression of a wide variety of xenobiotic biotransforming enzymes whose common underlying feature is their ability to catalyse the oxidation, reduction and hydrolysis (Phase I) and/or conjugation (Phase II) of functional groups on drug and chemical molecules. The broad substrate specificity, isoenzyme multiplicity and inducibility of many of these enzyme systems make them particularly well adapted to handling the vast array of different chemical structures in the environment to which we are exposed daily. However, some chemicals may also be converted to more toxic metabolites by certain of these enzymes, implying that variations in the latter may be important predisposing factors for toxicity. Pharmacogenetic defects of xenobiotic biotransformation enzymes, a subclass of inborn errors of metabolism which are manifested only upon drug challenge, introduce marked variation into human populations for the pharmacokinetics and pharmacodynamics of therapeutic and toxic agents, and thus may have important clinical consequences for drug efficacy and toxicity.

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Section: Drug Biotransformation Reactionsmentioning

confidence: 99%

Detoxification pathways in the liver

Grant

1991

J of Inher Metab Disea

143

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“…Our observation that the urinary metabolite profile of caffeine in both young and elderly men is not affected by the route of administration, nor by the order in which the subjects received their oral and intravenous doses of caffeine indicates that the previous suggestion (Birkett et al, 1983;Arnaud, 1984) indicate that the dimethyluric acids are not demethylated to produce monomethylurates. 1,3,7-DAU(ADMU) = 6-amino-5-[N-formylmethylamino]-1,3-dimethyluracil; 3,7-DAU = 6-amino-5-[N-formylmethylamino]-1-methyluracil; 1,7-DAU = 6-amino-5-[N-formylmethylamino]-3-methyluracil.…”

Section: Discussionmentioning

confidence: 47%

Comparison of the urinary metabolite profile of caffeine in young and elderly males.

Blanchard¹,

Sawers²,

Jonkman³

et al. 1985

Brit J Clinical Pharma

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The urinary metabolite profile of caffeine was compared in a group of seven healthy young men aged 18‐29 years and in a group of five healthy elderly men aged 66‐71 years. All subjects were given 5 mg/kg doses of caffeine as an aqueous oral solution or an intravenous infusion on two separate occasions in a randomized crossover design. Urine samples were collected for 24 h after dosing and analysed for caffeine and eleven of its metabolites by high‐performance liquid chromatography. The effects of age, route of administration, and order of administration by route on the metabolite profile of caffeine were examined. The route of administration and the order of administration by the two routes were found not to influence the urinary metabolite pattern significantly. The urinary metabolite profile did not vary substantially with age except for the observation that significantly greater amounts of 1‐ methyluric acid, 7‐methyluric acid and 1,7‐dimethyluric acid were excreted by the elderly subjects.

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“…4). Qualitative similarities between the rabbit and other species in the metabolism of 1,3-DMX were confirmed (7,10,(22)(23)(24)(25)(26)(27)(28), and suggested that the same enzyme system is involved in the 1,3-DMX metabolism in the species concerned. Quantitative comparisons with previous studies in rabbits are not possible because the only report up to now was in 1951 (29), when knowledge and analytical methods were less refined.…”

Section: Resultsmentioning

confidence: 66%

“…Disposition of 1,3-DMX has been widely investigated both in animals and humans, and in different physiopathological conditions (6). The compound, like other xanthines, is eliminated by animals and humans through hepatic biotransformation, catalyzed by the cytochrome P-450-dependent microsomal enzymes, to several metabolites ( anthines (l-methylxanthine, I-MX; 3-methylxanthine, 3-MX); uric acids (1,3-dimethyluric acid, 1,3-DMU; l-methyluric acid, I-MU; 3-methyluric acid, 3-MU) and aminouracil compounds (6-amino-5-[N-formylamino] 1,3-dimethyluracil, 1,3-DAU; 6-amino-5-[N-formylamino] 3-methyluracil, 3-MAU; 6-amino-5-[N-formylamino] I-methyluracyl, I-MAU) (7). Studies to date in humans and animals have been mainly based on the determination of general kinetic and metabolic profiles of 1,3-DMX.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of theophylline and its metabolites in rabbits

Celardo

Traina

Jankowski

et al. 1985

European Journal of Drug Metabolism and Pharmacokinetics

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The pharmacokinetics of theophylline (1,3-DMX) and its metabolites were investigated in detail in four male rabbits after bolus intravenous injection (12 mg/kg) of the compound. Theophylline was measured in blood and urine, and its metabolites were determined only in urine. Apparent first-order rate constants for the metabolic processes involved in the formation of 1,3-DMX metabolites and their excretion in urine were calculated. An appropriate 13-compartment model was formulated to describe the disposition of 1,3-DMX and its metabolites.

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Products of Metabolism of Caffeine

Cited by 38 publications

References 108 publications

Detoxification pathways in the liver

Detoxification pathways in the liver

Comparison of the urinary metabolite profile of caffeine in young and elderly males.

Pharmacokinetics of theophylline and its metabolites in rabbits

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