Caffeine as a potential indicator for acetylator status

The identification of patients as 'fast acetylators' or 'slow acetylators' is used in clinical practice to help recognize those at risk from toxicity and in guiding the dosage of N-acetylated drugs. Caffeine has been proposed as a marker for drug acetylation on the basis of a ratio of urinary metabolites (5-acetylamino-6-formylamino-3-methyl uracil and 1-methylxanthine, AFMU:MX) determined by high-performance liquid chromatography. The caffeine test was studied in 26 subjects by reference to the use of sulphamidine as the test substance. The distribution of urinary AFMU:MX ratios allowed assignment of subjects to 'slow' and 'fast' acetylator status (AFMU:MX less than 2.1 and greater than 2.3 respectively). The results showed accordance with those from the sulphadimidine test with the exception of one subject. The possible interference of concurrent administration of sulphadimidine (as an example of a drug known to undergo metabolism by N-acetylation) was also studied in 11 of the subjects. The interference was found to be small (apparent mean bias 11%) but of possible clinical significance.