In the present study the effect of metastatic
liver disease on hepatic
drug metabolism has been examined by studying the pharmacokinetics of
antipyrine and the urinary excretion of
antipyrine and its three major metabolites (4-hydroxyantipyrine,
norantipyrine, and 3-hydroxymethylantipyrine) in 12 patients with extensive metastatic
liver disease, and in 12 matched healthy controls. In the patients total liver volume, the volume of the liver parenchyma, and the volume of the liver
metastases were determined by computed tomography. The volume of liver
metastases always exceeded 35% of the total liver volume. There were no significant differences between the patients and controls in plasma half-life, plasma clearance, or apparent volume of distribution of
antipyrine. The cumulative urinary excretion of
antipyrine and its three major metabolites was significantly lower in patients [44 (18) %] than in controls [71 (8) %]. The excretion of
antipyrine itself was unchanged and the decrease in cumulative excretion was due to reduced excretion of the three metabolites. The results show that the activity of the hepatic
mixed function oxidases was not impaired even in patients with extensive metastatic
liver disease. This may be because liver
metastases do not cause a corresponding reduction in the volume of normal hepatic parenchyma. The decreased urinary excretion of the three major metabolites of
antipyrine, which are mainly glucuronidated, may have been due to an alteration in the process of conjugation.