AMINOPYRINE METABOLISM IN MAN - THE ACETYLATION OF AMINOANTIPYRINE COSEGREGATES WITH ACETYLATION OF CAFFEINE

Aminopyrine and caffeine metabolism was evaluated in vivo in 21 health y volunteers in order to elucidate whether the acetylation capacity of the two substances correlates. The ratio of the aminopyrine metabolit es 4-acetyl-aminoantipyrine (AAA)/4-aminoantipyrine (AA) was compared with the ratios of caffeine metabolites AAMU/1-X and AAMU/(AAMU + 1-X + 1-U). All the subjects phenotyped as slow acetylators with caffeine displayed AAA/AA ratios lower than 3.4, whereas the extensive acetylat ors had ratios higher than 3.8. Therefore, the acetylator phenotype de termined with caffeine cosegregated with the capacity to acetylate the aminopyrine metabolite AA. The N-demethylation of aminopyrine and caf feine correlated strongly in the subjects studied (p < 0.001). A highl y significant correlation (r = 0.92;p < 0.001) was also observed betwe en caffeine N(1)- and N(7)-demethylation activities. In addition, most N-demethylation steps of both drugs significantly correlated, suggest ing partial contributions by identical or closely related enzymes in t heir metabolism.