Relationship between metabolic clearance rate of antipyrine and hepatic microsomal drug-oxidizing enzyme activities in humans without liver disease

Abstract

The aim of this study was to look for correlations between the metabolic clearance rate of antipyrine and (a) the concentration of cytochrome P-450, and (b) the NADPH cytochrome c reductase, aminopyrine demethylase, and aniline hydroxylase activities in the liver microsomes of 20 patients without liver disease. The results confirmed interindividual differences in the values of in vivo and in vitro assessments of hepatic drug metabolism. No significant correlation appeared in this group of patients between the metabolic clearance rate of antipyrine and the microsomal amount of cytochrome P-450, whereas the metabolic clearance rate of antipyrine exhibited a significant relationship to the NADPH cytochrome c reductase (p < 0.05), aminopyrine demethylase (p < 0.05), and aniline hydroxylase (p < 0.02) activities. These results suggest that the metabolic clearance rate of antipyrine: (a) is not strictly related to the amount of cytochrome P-450 in hepatic microsomes; and (b) although significantly related to the activity of hepatic drug-metabolizing enzymes, does not have a predictive value to assess the enzyme equipment of liver microsomes in a given normal subject.