Further studies of metyrapone effects upon anilide hydroxylation.
Drug Metab Dispos 1975 Nov; 3(6):507-512
Procedures for the determination of phenolic products, and the effects of metyrapone (54364) and related compounds on anilide hydroxylation were investigated. Adult male Holtzman-rats and New- Zealand-White-rabbits, pretreated for 3 days with sodium- phenobarbital (57307), were used for preparation and reconstitution of lyophilized liver fractions. The formation of acetaminophen (103902) from acetanilide (103844) in rat and rabbit liver homogenate was demonstrated by gas chromatography of extracts of incubation mixtures. Hydrolysis of acetaminophen was minimally inhibited by an 0.4 millimolar concentration of metyrapone in rat and rabbit liver preparations. The formation of acetaminophen from acetanilide was enhanced 2 fold in rat liver homogenate in the presence of an 0.4 millimolar concentration of metyrapone; the production of p-aminophenol (123308) was not affected. In rabbit liver, the formation of acetaminophen was inhibited by 80 percent by an 0.4 millimolar concentration of metyrapone. Para-aminophenol production from the homologous series of formanilide (103708), acetanilide and propionanilide (620713) was greatest from formanilide and least from propionanilide. While the hydroxylation of acetanilide in the rat liver preparation was enhanced with a maximum at an 0.4 millimolar concentration of metyrapone, the hydroxylation of other anilides was inhibited. Alpha,alpha'- dipyridyl (366187) enhanced phenol production from carbonacylanilides but did not affect phenol production from methane- sulfonanilide (1197224). The authors conclude that this indicates that the mechanism of enhancement of anilide hydroxylation by these modifiers is different.
NIOSH-Publication; NIOSH-Grant; Grants-other; Animal-studies; Liver-cells; Chemical-properties; Bioassays; Dose-response; Metabolic-study; Enzyme-activity; Biosynthesis; Phenolic-compounds
Pharmacology and Therapeutics Univ of Florida Coll of Med Dept of Pharma & Therapeutics Gainesville, Fla 32601
54-36-4; 57-30-7; 103-90-2; 103-84-4; 123-30-8; 103-70-8; 620-71-3; 366-18-7; 1197-22-4
Other Occupational Concerns; Grants-other
Drug Metabolism and Disposition
University of Florida Gainesville, Gainesville, Florida