Human metabolism of antipyrine labelled with 14C in the pyrazolone ring or in the N-methyl group.

After ingestion of [N-14CH3]antipyrine by two healthy male subjects, the urinary recoveries of radioactivity plus norantipyrine (non-radioactive) were 63 and 73%. After ingestion of [3-14C]antipyrine in the same two subjects, the urinary recoveries of radioactivity were 84 and 99%. Therefore, N-demethylated metabolites which have not been identified before, besides norantipyrine, must account for 21--26% of the dose. Serum half-lives of total 14C were about 50% greater than those of unchanged antipyrine. The difference was less in the saliva. Three major metabolites of antipyrine, norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine, in urine were determined by radio-t.l.c. and g.l.c. These three metabolites and antipyrine accounted for 50--69% of the administered dose. The urinary excretion half-lives of these three metabolites were similar to each other and to the serum half-life of antipyrine. 3-Hydroxymethylantipyrine in one subject was excreted more slowly than the other metabolites. The radioactive metabolite not extracted from urine by organic solvents was very polar, as judged by t.l.c.