The effect of anti-cancer drugs on the plasma disposition of antipyrine and the biliary excretion of phenolphthalein in the rat

Microsomal Metabolism of Antipyrine in Rats Treated with Antineoplastic Drugs

“…the lat ter effect probably being enhanced by such factors as fasting and stress. In vitro data indicate a normal overall rate of antipyrine metabolism, but enhancement of specific en zyme activities [1]. Since activation of car cinogens is known to be mediated by micro somal monooxygenases, and hepatomas are reported in patients treated with methotrex ate [18], further investigations should be un dertaken of specific patterns of drug metabo lites and different microsomal monooxygen ase enzyme activities after pretreatment with antineoplastic drugs.…”

“…The 4-hydroxy-antipvrine is probably formed via the cytochrome P-448 whereas another cytochrome, whose activity is not influenced by 3-methvlcholanthrene, is in volved in the formation of 3-hydroxy-methyl-antipyrine [13]. The notion that cyto chrome P-448 plays a role in the formation of 4-hydroxy-antipyrine is supported by the ob servation of a close correlation between the rate of hydroxylation of benzo-a-pyrene and the rate of 4-hydroxylation of antipyrine in human liver [17], Since an increase of benzoa-pyrene hydroxylase activity was found in rats pretreated with antineoplastic agents [1], it is suggested that 4-hydroxy-antipyrine me tabolism could be induced by the present pre treatment schedule.…”

“…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.Changes in antipyrine disposition after pretreatment of rats with antineoplastic drugs were first reported by Capel et al [ 1 ]. in a study using pooled antipyrine plasma con centrations from groups of rats killed at dif ferent intervals after oral antipyrine dosing.…”

“…The purpose of the present investigation was to study microsomal antipyrine metabo lism in fed, unrestrained rats pretreated with antineoplastic drugs in a dosing regimen identical with that of the in vivo studies [1,2], Michaelis-Menten parameters were calcu lated from microsomal antipyrine metabo lism and transformed to terms equivalent to those used for quantitation of in vivo rate of metabolism, e.g. intrinsic clearance [7] and total clearance.…”

Synthesis and Characterization of Spin-Free [Co2(N,N′-Tetra(4-antipyrylmethyl)-1,2-diaminoethane)Cl4]

“…6 were used as external standard and as instrument lock. Solution magnetic moments (") were measured by Evans' method [11] using the solvent methanol for temperature calibration [12].…”