Aminopyrine metabolism in the presence of hyperbilirubinemia due to cholestasis or hepatocellular disease. Combined use of laboratory tests to study disease-induced alterations in drug disposition.

Hepatocellular diseases, such as hepatitis, cirrhosis, or hepatic neoplasm, are associated with impaired metabolism of certain drugs, including aminopyrine, whereas cholestasis produced variable effects on aminopyrine metabolism. Reasons for the variable effects of cholestasis on hepatic aminopyrine metabolism were sought by performing in patients with hyperbilirubinemia the aminopyrine breath test (ABT), which consists of measurements of 14CO2 in breath 2 hr after oral administration of [14C]aminopyrine. Hyperbilirubinemia (total serum bilirubin less than 1.2 mg/100 ml) in these patients was due to hepatocellular disease or cholestasis. The ABT, defined as the percentage of the administered dose of 14C excreted in breath for 2 hr after [14C]aminopyrine administration, was 6.2 +/- 0.8% (mean +/- SD) in 107 control patients with normal total serum bilirubin. The ABT was severely abnormal (less than 3.1%) in 54 of 77 hyperbilirubinemic patients (70%) with hepatocellular disease and normal (greater than 4.5%) in only 5 of these patients (6%). In contrast, the ABT was severely abnormal in only 1 of 40 cases of cholestasis with hyperbilirubinemia and normal in 70% of these patients. Thus, aminopyrine metabolism is normal in most cases of hyperbilirubinemia due to cholestasis and is only rarely severely abnormal in these patients. On the other hand, severe abnormality in aminopyrine metabolism occurs in the majority of patients with hyperbilirubinemia due to hepatocellular disease. It therefore appears that the ABT may be useful in hyperbilirubinemia to distinguish patients with hyperbilirubinemia due to cholestasis form most patients with hyperbilirubinemia due to hepatocellular disease.