Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r2 = 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.

Background. The influence of cancer on antipyrine metabolism is under debate. Methods. To assess the functional activity of a liver with solid metastases from primary colorectal cancer, antipyrine metabolism was studied after the drug was administered orally (18 mg/kg body weight) to 55 healthy volunteers, 62 patients with well‐compensated cirrhosis, and 42 patients with small (Class A) or massive (Class B) metastatic liver involvement. Results. In patients with cancer, antipyrine clearance (0.472 ± 0.177 ml/min/kg) was similar to that in healthy volunteers (0.456 ± 0.198 ml/min/kg) and significantly higher than in those with cirrhosis (0.259 ± 0.17 ml/min/kg, P < 0.001). There was no difference in antipyrine pharmacokinetics between Class A and B involvement. In the entire population, antipyrine clearance was correlated with serum albumin levels (r = 0.294, P = 0.000∼) and prothrombin activity (r = 0.416, P = 0.001). This positive correlation was not present when only the neoplastic group was considered. No correlation was found between antipyrine clearance and alkaline phosphatase levels. In patients with cancer, no relationship was found between antipyrine clearance and carcinoembryonic antigen and lactic dehydrogenase levels. Conclusions. These results show that patients with livers largely replaced by solid metastases are able to metabolize antipyrine to the same extent as healthy subjects.

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