The effect of age on antipyrine metabolism by liver microsomes isolated from phenobarbital-treated rats

A study was performed to test the hypothesis that ageing influences the activities of diverse forms or populations of cytochrome P-450 isoenzymes in different ways. The formation of antipyrine metabolites in induced rats is mediated by such different forms or populations of cytochrome P-450 isoenzymes. To test the hypothesis, the formation rates of antipyrine metabolites by liver microsomes isolated from phenobarbital-treated rats of different ages was determined. After phenobarbital induction in vitro, the maximal velocity for norantipyrine formation decreased from 12 to 24 months and then showed a tendency to increase with age. Hydroxymethylantipyrine formation did not change with age. 4-Hydroxyantipyrine increased between 3 and 12 months and remained constant afterwards. This is in agreement with data obtained in vivo in uninduced male BN/BiRij rats. It can be concluded that age does indeed influence the activities of different forms or populations of the cytochrome P-450 isoenzymes in different ways. Consequently, determining the overall clearance of antipyrine, which is metabolized by several isoenzymes, especially in the induced situation, is not to be recommended for measuring the activity of cytochrome P-450 isoenzymes as a function of age.