Assessment of a simple method for acetylator phenotyping with caffeine.

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Abstract
A simple method for acetylator phenotyping with caffeine was studied. Three hundred milligrams of caffeine was given orally to 39 consanguineously unrelated healthy Japanese subjects and urine was collected over 24 hr. 5-Acetylamino-6-formylamino-3-methyluracil (AFMU) is formed by acetylation ; four other major metabolites [1-methylxanthine (1X), 1-methyluric acid (1U), 1, 7-dimethylxanthine (17X), and 1, 7-dimethyluric acid (17U)] are formed by oxidation. Their urinary concentration was measured by HPLC. The frequency histogram of 24 hr urinary molar. excretion ratio of AFMU to 1 X (AFMU/1 X) showed a bimodal distribution as well as AFMU to total major metabolites [AFMU/ (1X+1U+17X+17U+AFMU)]. Five of 39 subjects (12.8%) were determined to be slow acetylators by AFMU/ (1X+1U+17X+17U+AFMU) and were identical to those of slow acetylator considered by AFMU/1X. A similar bimodality was also shown in the distribution of AFMU/1X using pooled 2 hr urine (2 to 4 hr after ingestion of caffeine). Concordance for slow acetylators was also observed between AFMU/1X using pooled 2 hr urine and AFMU/ (1X+1U+17X+17U+AFMU) using pooled 24 hr urine. These results indicate that an individual acetylator phenotype could be determined by AFMU/1X of pooled 2 hr urine.

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