Antipyrine clearance and metabolite formation in patients with alcoholic cirrhosis

The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age 37-70 years) and 17 healthy subjects (age 28-55 years). Liver volume was also measured and was found to be larger in patients than in controls, mean values being 1.86 and 1.36 l respectively. The elimination half-life of antipyrine in patients with alcoholic liver cirrhosis was significantly longer than in the healthy subjects (P less than 0.001). Mean values were 39.9 and 10.1 h respectively. Alcoholic liver cirrhosis had no effect on the apparent volume of distribution of antipyrine, but antipyrine plasma clearance was substantially reduced in the patients. Mean clearance values (ranges) were 13.5 (9.3-22.8) ml/min in the patients and 49.3 (31.1-103) ml/min in healthy subjects. Normalization of antipyrine plasma clearance for liver volume resulted in an only slightly increased distinction between patients and healthy subjects, mean values (ranges) being 7.8 (3.3-13.0) ml min(-1) 1(-1) and 36.1 (21.9-35.9) ml min(-1) 1(-1) respectively. The cumulative renal excretion of 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) was significantly lower in patients with alcoholic liver cirrhosis than in healthy subjects, as was the total recovery of antipyrine and major metabolites from urine. Mean values were 15.0, 8.4 and 41.2% of dose in the patients respectively and 24.3, 25.8 and 68.9% of dose in the control subjects. Excreted amounts of total and unconjugated 3-hydroxymethylantipyrine (HMA) and of unchanged antipyrine were the same in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)