Microsomal metabolism of antipyrine in rats treated with antineoplastic drugs

Pretreatment with antineoplastic drugs for at least 1 week is known to reduce in vivo metabolic clearance of antipyrine in rats tested after 24 h of fasting and restraining. In this study hepatic metabolism of 14C-antipyrine was investigated in 9,000 g supernatants of fed, unrestrained rats pretreated with cyclophosphamide, 5-fluorouracil or methotrexate. Total antipyrine metabolites formed were measured by a radiometric assay. Apparent Vmax and Km values were estimated and transformed to intrinsic (hepatic) clearance and total (body) clearance for comparison with in vivo terms of metabolic rate. Hepatic microsomal metabolism of antipyrine in control rats expressed as intrinsic clearance, 0.12 +/- 0.03 ml (g liver min)-1, and total clearance, 4.8 +/- 1.2 ml (kg body wt min)-1, was not significantly changed after antineoplastic pretreatment, indicating that the previously observed inhibitory action of these drugs on in vivo antipyrine metabolism may be modulated by factors such as fasting and stress.