Antipyrine elimination and hepatic microsomal enzyme activity in patients with liver disease.
Induction of hepatic monooxygenases reflected by 7-ethoxycoumarin O-deethylase has been proposed to be associated with the initiation of liver damage. This study investigated a possible correlation between 7-ethoxycoumarin O-deethylase, reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase and benzypyrene hydroxylase activity in liver biopsy specimens of 31 patients with liver disease and antipyrine elimination, an in vivo parameter of hepatic monooxygenase activity. No correlation was found between the enzyme activities and antipyrine clearance or half-life. When microsomal enzyme activities were compared with the formation rate of 4-hydroxyantipyrine, 3-methylhydroxyantipyrine, and norantipyrine, a correlation was found only between benzo[alpha]pyrene hydroxylase and 3-methylhydroxyantipyrine (r = 0.89; p less than 0.0005). There was also a correlation between 7-ethoxycoumarin O-deethylase and reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase (0.56; p less than 0.05). Our data suggest that antipyrine elimination is not related to 7-ethoxycoumarin O-deethylase activity in liver disease. However, the formation rate of antipyrine metabolites, rather than antipyrine half-life and clearance, may correlate with the activity of certain microsomal enzymes.
Wensing
G
G
I. Medizinische Klinik, Christian-Albrechts-Universität Kiel, West Germany.
Ohnhaus
E E
EE
Hoensch
H P
HP
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000983:Antipyrine / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology*; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012044:Regression Analysis
D015660:7-Alkoxycoumarin O-Dealkylase; D009251:NADPH-Ferrihemoprotein Reductase; D000983:Antipyrine