The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects

Aims  To establish whether gender or N‐acetyltransferase 2 (NAT2) genotype influence the urinary 17 U+17X/137X ratio after dosing with caffeine. Methods  Ninety‐two nonsmoking individuals underwent caffeine phenotyping. NAT2 genotype was determined by the polymerase chain reaction followed by a rest...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2000-03, Vol.49 (3), p.240-243
Main Authors: Welfare, Mark R, Bassendine, Margaret F, Daly, Ann K
Format: Article
Language:English
Subjects:
Adolescent
Adult
Arylamine N-Acetyltransferase - genetics
Arylamine N-Acetyltransferase - metabolism
Biological and medical sciences
caffeine
Caffeine - metabolism
Central Nervous System Stimulants - metabolism
CYP1A2
Cytochrome P-450 CYP1A2 - metabolism
Drug Disposition
Female
General pharmacology
Genotype
Humans
Male
Medical sciences
Middle Aged
NAT2
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Polymorphism, Genetic
Sex Characteristics
Smoking
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Summary:Aims  To establish whether gender or N‐acetyltransferase 2 (NAT2) genotype influence the urinary 17 U+17X/137X ratio after dosing with caffeine. Methods  Ninety‐two nonsmoking individuals underwent caffeine phenotyping. NAT2 genotype was determined by the polymerase chain reaction followed by a restriction digest (PCR‐RFLP). Results  The median ratio for urinary 17 U+17X/137X was 6.7 (range 1.45–18.65). 55% of subjects were slow acetylators. Gender did not affect the metabolic ratio or NAT2 genotype. Mean 17 U+17X/137X ratio differed between fast (6.75) and slow (8.69) acetylators (95% CI for the difference, 0.32–3.56). Conclusions  The findings are further evidence that the 17 U+17X/137X urinary ratio is not a robust measure of CYP1A2 activity. A possible mechanism by which the ratio might be influenced by NAT2 genotype is suggested.
ISSN:0306-5251
1365-2125
DOI:10.1046/j.1365-2125.2000.00130.x