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PubMed1983

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.

Adult↗
PubMed1975

[Non-HL-A specific autoantibody against granulocytes, lymphocytes and thrombocytes in a patient with agranulocytosis due to pyrazolone].

An antibody of hitherto unknown specificity has been found in the serum of a patient who suffered three episodes of agranulocytosis after ingestion of aminopyrine derivatives. In vitro, the antibody reacts not only with homologous and autologous granulocytes and thrombocytes. It belongs to the IgM class and absorption of the serum with earlier leukocytes or platelets eliminates the activity against all three cell types. An HL-A specificity (LA or Four locus) can be ruled out, since all tests are positive with cells of individuals differing from the patient in all four HL-A specificities. Addition of the patient's serum results in marked reduction of thymidine uptake in the mixed leukocyte culture as well as during stimulation of lymphocytes with phytohemagglutinin or PPD; however, almost no effect is observed on stimulation with small amounts of Pokeweed mitogen. The rosette formation of lymphocytes with sheep erythrocytes or sensitized human erythrocytes is not influenced by this serum. This pattern is comparable to what is known for alpha-methyl-dopa-induced autoimmune hemolytic anemia insofar as the antibody does not require the presence of the offending drug for its action.

Agranulocytosis↗