An alternative test for acetylator phenotyping with caffeine.
Previously published methods allow the determination of the genetically controlled acetylator status using caffeine as a test drug, based on the urinary excretion of a ring-opened metabolite of caffeine, an acetylated uracil (5-acetylamino-6-formylamino-3-methyluracil). 5-Acetylamino-6-formylamino-3-methyluracil is labile but can be converted into a stable, deformylated product referred to as 5-acetylamino-6-amino-3-methyluracil, which has recently been shown to be quantifiable by exclusion chromatography. The first part of the present article represents a longitudinal study of three subjects to assess the intraindividual variability of those caffeine metabolite ratios that are of potential interest for the determination of acetylator phenotypes. Effects of single and multiple doses, as well as of different periods of urine collection, were tested. A ratio relating the excretion of 5-acetylamino-6-amino-3-methyluracil to that of all products of the 7-demethylation pathway of paraxanthine proved to be highly reproducible, particularly after collection of overnight urine after coffee consumption during the day. This ratio showed complete concordance with the plasma index for sulfamethazine acetylation. The second part of this article showed the use of this ratio in a population study. It allowed a good separation of slow and fast acetylators and probably also a separation of homozygous and heterozygous fast acetylators.
Tang
B K
BK
Department of Pharmacology, University of Toronto, Ontario, Canada.
Kadar
D
D
Kalow
W
W
D000107:Acetylation; D002110:Caffeine / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008722:Methods; D010641:Phenotype; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine
D002110:Caffeine; D014498:Uracil; C036692:5-acetylamino-6-formylamino-3-methyluracil; C054188:5-acetylamino-6-amino-3-methyluracil