Accuracy and clinical utility of simplified tests of antipyrine metabolism

Abstract

High-performance liquid chromatography (h.p.l.c.) was used to measure plasma antipyrine concentrations in sixteen healthy subjects; five males, six females taking oral contraceptive steroids (OCS) and five age-matched females not taking OCS. Following oral administration of the drug, antipyrine clearance could be determined with similar precision and accuracy from plasma concentrations at two selected times (4 h and 24 h) ('two-sample antipyrine clearance test') as from six samples taken over two to three elimination half-lives (t1/2) of the drug ('conventional antipyrine clearance test'). Provided times for plasma sampling were modified appropriately, the two-sample antipyrine clearance test also gave reliable results in four patients taking phenytoin (sampling times 4 h and 8 h) who had significantly enhanced antipyrine clearance, and in nine patients with severe liver disease (using 4 h and 48 h) in whom antipyrine clearance was impaired. Urinary excretion of antipyrine metabolites (from 0-24 h) was determined in the above groups. Antipyrine systemic clearance correlated best with the percentage of administered dose excreted as 4-hydroxyantipyrine (r = 0.66, P less than 0.001) but also with 3-hydroxymethylantipyrine (r = 0.54, P less than 0.001) and with total metabolites excreted (r = 0.60, P less than 0.001). Total antipyrine metabolites excreted in urine in 24 h were significantly different from controls only in patients with liver disease (14 +/- 7.6% of administered dose vs 62 +/- 14%, P less than 0.001). The relative proportion of antipyrine metabolites did not appear to be altered when hepatic mixed function oxidation was induced by phenytoin or inhibited by OCS or by severe liver disease.