Metabolic fate of N-γ-phenylpropyl-n-benzyloxy acetamide (w-1372) in rats, dogs, and monkeys

✍ Scribed by Jerome Edelson; J. F. Douglas; B. J. Ludwig

• Publisher: John Wiley and Sons
• Year: 1970
• Tongue: English
• Weight: 300 KB
• Volume: 59
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600590520

✦ Synopsis

The absorption, distribution, and metabolic fate of N-7-phenylpropyl-N-benzyloxy acetamide (W-1372) was studied in the rat, dog, and monkey. W-1372-14C was readily absorbed by all three species. Following an oral dose, peak blood levels of radioactivity were attained within 1 hr. in the monkey and in 2 hr. in the dog. The blood half-life of radioactivity following oral administration was 11.5 hr. in the dog. In the rat, maximum blood concentration of 14C was reached 1 hr. following intraperitoneal administration, and the half-life was about 2 hr. Distribution studies of labeled drug in the rat indicate that the administered radioactivity is largely excreted within 24 hr. The major metabolites of W-1372 are hippuric acid, benzoic acid, N-7-phenylpropyl-Nbenzyloxyamine, and carbon dioxide. Keyphrases 0 N-7-Phenylpropyl-N-benzyloxy acetamide (W-1372)--metabolism I J Absorption, distribution, metabolic fate-W-1372-14C Inverse isotope dilution-analysis Hippuric acid, benzoic acid, N-7-phenylpropyl-N-benzyloxyamine, carbon dioxid-W-1372-14C metabolites TLC-identification IR spectrop hotometry-identification N-y-Phenylpropyl-N-benzyloxy acetamide (W-1372) is a new hypolipidemic agent that has been shown by Berger et al. (1, 2) to reduce the extent of atherosclerotic lesions and to lower serum cholesterol levels in animals maintained on a high-cholesterol diet. This manuscript describes studies from this laboratory on the absorption, distribution, and metabolic fate of W-1372 in the rat, dog, and squirrel monkey.