ArticleEuropean journal of clinical pharmacology2004
Phenotyping of N-acetyltransferase type 2 by caffeine from uncontrolled dietary exposure.
Article in European journal of clinical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Mesalazine pharmacokinetics and NAT2 phenotype.European journal of clinical pharmacology · 2009Trial
- Determination of Urinary Caffeine Metabolites as Biomarkers for Drug Metabolic Enzyme Activities.Nutrients · 2019Article
- Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1.Biochemical pharmacology · 2018Article
- Urine excretion of caffeine and select caffeine metabolites is common in the U.S. population and associated with caffeine intake.The Journal of nutrition · 2015Article
- PharmGKB summary: very important pharmacogene information for N-acetyltransferase 2.Pharmacogenetics and genomics · 2014Review
- Phenotyping of N-acetyltransferase type 2 and xanthine oxidase with caffeine: when should urine samples be collected?European journal of clinical pharmacology · 2009Article
- The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine.The pharmacogenomics journalArticle
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Authors and funding
11 authors.
Funding
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Abstract
BACKGROUND AND
objectiveThe standard approach for phenotyping of the human arylamine N-acetyltransferase 2 (NAT2) uses urinary caffeine metabolite ratios after a caffeine test dose taken in after methylxanthine abstinence. We tested whether these standardization measures were still needed when a more sensitive quantification technique was used.
methodsA new liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the quantification of the caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 5-acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1X), and 1-methylurate (1U) was developed. Urine samples from 77 healthy volunteers collected before and 5-6 h after oral intake of 150-200 mg caffeine were analyzed. The lower limits of quantification were 0.1 microg/ml for caffeine, 1X, 1U, and AFMU, and 0.2 microg/ml for AAMU.
resultsThe urinary NAT2 ratios (AFMU+AAMU) / (AFMU+AAMU+1X+1U) before and after caffeine intake correlated well in 65 volunteers (r(2)=0.827; P< 0.0001). In 12 participants (16%), metabolite concentrations in urine before caffeine intake were below the quantification limit. NAT2 genotyping, done in 41 volunteers for four SNPs, corroborated the phenotyping results.
conclusionNAT2 activity can be determined from a spontaneous urine probe in most subjects by quantification of caffeine metabolites arising from non-standardized dietary caffeine exposure using LC-MS/MS. This may facilitate the phenotyping procedure.
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