Linked Life Data

8738764

Source:http://linkedlifedata.com/resource/pubmed/id/8738764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-10-25
pubmed:abstractText
Caffeine metabolism via the 3-demethylation pathway is sequentially catalyzed by cytochrome P4501A2 (CYP1A2), xanthine oxidase, and N-acetyltransferase. The activities of the three enzymes can be estimated from urinary metabolic ratios of four caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methyluric acid (1MU), 1-methylxanthine (1MX), and 1,7-dimethyluric acid (17DMU), after the ingestion of caffeine. A method for quantitation of the four metabolites in human urine has been developed. The method is based on a one-step extraction with ethyl acetate/2-propanol followed by high-performance liquid chromatography with UV detection. The detection limit was 1 microM for AFMU, 1MU, and 1MX and 2 microM for 17DMU. The intraday and interday coefficients of variation were < 3% and < 7%, respectively, and the accuracy was within +/- 3%. The method was employed in a population study of 277 healthy volunteers, each of whom ingested 200 mg caffeine and provided a urine sample approximately 6 h later. The metabolite concentration ranges in the urines were 2.1-327 microM, 4.0-744 microM, 4.9-598 microM, and 6.4-260 microM for AFMU, 1MU, 1MX, and 17DMU, respectively. The CYP1A2 ratio (AFMU + 1MU + 1MX/17DMU) was significantly lower in women than in men, excluding smokers and oral contraceptive users. The CYP1A2 ratio was higher in smokers than in nonsmokers, confirming the induction of CYP1A2 by smoking. In women using oral contraceptives, the CYP1A2 ratio was, as expected, significantly lower than in women not using oral contraceptives. For the N-acetyltransferase ratio (AFMU/1MX) and the xanthine oxidase ratio (1MU/1MX), no differences were seen in terms of sex, smoking habits, or the use of oral contraceptives. All results are in agreement with previous reports on CYP1A2, N-acetyltransferase, and xanthine oxidase activities in humans. Thus, the method is both analytically and biologically reliable for the assessment of CYP1A2, N-acetyltransferase, and xanthine oxidase in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0163-4356
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
254-62
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8738764-Acetyltransferases, pubmed-meshheading:8738764-Adolescent, pubmed-meshheading:8738764-Adult, pubmed-meshheading:8738764-Biotransformation, pubmed-meshheading:8738764-Caffeine, pubmed-meshheading:8738764-Central Nervous System Stimulants, pubmed-meshheading:8738764-Chromatography, High Pressure Liquid, pubmed-meshheading:8738764-Contraceptives, Oral, Hormonal, pubmed-meshheading:8738764-Cytochrome P-450 CYP1A2, pubmed-meshheading:8738764-Drug Interactions, pubmed-meshheading:8738764-Female, pubmed-meshheading:8738764-Humans, pubmed-meshheading:8738764-Male, pubmed-meshheading:8738764-Reproducibility of Results, pubmed-meshheading:8738764-Sex Characteristics, pubmed-meshheading:8738764-Smoking, pubmed-meshheading:8738764-Spectrophotometry, Ultraviolet, pubmed-meshheading:8738764-Xanthine Oxidase
pubmed:year
1996
pubmed:articleTitle
Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans.
pubmed:affiliation
Department of Clinical Pharmacology, Odense University, Denmark.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't