Microsomal Metabolism of Antipyrine in Rats Treated with Antineoplastic Drugs

Abstract

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.

Effects of membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver of drugs: A microdialysis study in rats

“…16,17 The mean values of plasma CL were 97. and 15.0 ml/min/kg, respectively). [24][25][26][27] As shown in our previous study, 6 With the exception of propranolol unbound concentrations in liver, the unbound drug concentrations of all compounds reached a steady state in blood, liver and skeletal muscle within 2 h after the start of infusion. Thus, the steady state unbound concentrations were calculated as the average of unbound concentrations from 2 h up to 6 h time points.…”

“…The plasma Cl values of antipyrine, lamotrigine, digoxin, and carbamezapine (4.81, 1.48, 9.1, and 18.1 ml/min/kg, respectively) were consistent with the reported plasma CL values by other investigators (4.80, 0.830, 17.3, and 15.0 ml/min/kg, respectively). 24 , 25 , 26 , 27 …”