High incidence of multisystemic reactions to zimeldine

Summary Four metabolites of dipyrone, 4-methyl-aminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA) and 4-acetylamino-antipyrine (AAA) can be identified in human plasma after its oral administration. The plasma protein binding of the metabolites in samples from 20 healthy volunteers was determined by ultrafiltration. None of the metabolites were found to be extensively bound to plasma proteins. The binding of MAA and AA was relatively higher than of FAA and AAA, as expected from their chemical structure. The mean percentage plasma protein binding was 57.6% for MAA, 47.9 for AA, 17.8 for FAA and 14.2% for AAA. The correlation between the unbound concentration in plasma and the total concentrations of MAA, AA, FAA and AAA was linear. No association was evident between the total protein plasma concentration and the extent of binding. The possible therapeutic implications related to protein binding of several analgesic and non-steroidal anti-inflammatory drugs are discussed.