Antipyrine clearance and metabolite formation in primary biliary cirrhosis

The disposition of antipyrine is altered and may be a prognostic factor in the presence of various types of hepatic dysfunction. The object of the present study was to investigate whether antipyrine clearance and metabolite formation are useful to detect altered metabolic function in primary biliary cirrhosis. Saliva clearance of antipyrine and the formation clearance of antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) were investigated in a group of 34 women with biopsy-proven PBC (mean age 60 years; range 39-87 years) and in 15 healthy control women (mean age 62 years; range 46-78 years). Parameters of antipyrine clearance of patients in stage I and II were similar to those observed in healthy subjects. When compared to patients in stage I, patients in advanced stages showed a reduction in antipyrine clearance (-29% and -44% in stages III and IV, respectively) and increases in antipyrine half-life (+24% and +75% in stages III and IV, respectively). The reduction in antipyrine clearance was due to a reduction in the formation of all three antipyrine metabolites, with the formation clearance of both HMA and NORA decreasing to a slightly greater extent than that of OHA. Antipyrine clearance correlated significantly with serum bilirubin (P < 0.017) and the Mayo risk score (P < 0.001). Logistic regression analysis indicated that antipyrine clearance was an independent predictor of the histological stage of the disease (P < 0.001). Antipyrine clearance and metabolite formation is a sensitive parameter for assessing hepatic metabolic function in primary biliary cirrhosis.