Antilipidemic drugs. Part 4: The metabolic fate of the hypolipidemic agent isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-protionate (LF 178) in rats, dog and man

Arzneimittelforschung. 1976;26(5):896-901.

Abstract

The excretion and plasma concentrations of radioactivity and chromatographic patterns of radioactive components in plasma and excreta have been compared in rats, dogs and man after oral doses of the hypolipidemic agent isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl¿). 2. In rats, 48.1% of a single dose of 25 mg/kg was excreted in the urine, and 48.6% in the faeces. In dogs, 23.1% of a single dose at the same level was excreted in the urine, and 71.8% in the faeces, but 88.1% of a dose of 300 mg to man was excreted in the urine, and only 5.1% in the faeces. Peak levels of radioactivity in the plasma of all three species studied were similar (20--30 mug/ml) after doses at these levels and concentrations declined thereafter with half-lives of 7--24 h in rats and dogs, and 7 h in man. The half-life of radioactivity concentrations in rat plasma was not altered by repeated daily doses for 7 days. 3. Whole-body autoradiography of rats showed that radioactivity was largely associated with the liver, kidneys and gut, which are the organs of biotransformation and excretion, although relatively high levels were present in lungs and blood, and small amounts of radioactivity had a widespread distribution into some peripheral tissues during 2--7 h after dosing. 4. The available chromatographic evidence indicated that the most important biotransformation pathway appeared to be ester hydrolysis to LF 178 acid and formation of water soluble conjugates of this acid. This pathway appeared similar to that of the related drug clofibrate (ethyl p-chlorophenoxyisobutyrate).

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Animals
  • Autoradiography
  • Biotransformation
  • Chromatography, Thin Layer
  • Dogs
  • Female
  • Half-Life
  • Humans
  • Kinetics
  • Male
  • Propionates / metabolism*
  • Rats
  • Species Specificity

Substances

  • Propionates