Physiologic disposition and metabolism of an anti-ulcer agent, N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)-N',N'-dimethylurea, in rats, dogs, and monkeys

Drug Metab Dispos. 1982 Jan-Feb;10(1):28-34.

Abstract

14C-N-(2-Diisopropylaminoethyl)-N-(4,6-dimethyl-2-dimethyl- 2-pyridyl)-N',N'-dimethylurea (I) was administered orally to dogs and rats and to rhesus, African green, and squirrel monkeys. Radioactivity was excreted mainly in the urine (60-76%) of all species except the rat (25%). The plasma t1/2 of I in the dog was 0.8 hr. Five urinary metabolites were identified by TLC, GLC, GS/MS, and NMR spectrometry: N,N-dimethyl-N'-(2-diisopropylaminoethyl)-N'-(4-hydroxy-methyl-6-methyl-2-pyridyl)urea (II), N,N-dimethyl-N'-(2-diisopropylaminoethyl-N'-(4-methyl-6-hydroxymethyl-2-pyridyl )urea (III), N,N-dimethyl-N'-(2-isopropylaminoethyl)-N'-(4,6-dimethyl-2-pyridyl)urea (IV), N-methyl-N'-(2-diisopropylaminoethyl)-N'-(4,6-dimethyl-2-pyridyl)urea (V), and N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)urea (VI). II was a major urinary metabolite in dog and II and IV were major metabolites in the squirrel monkey. II was present in relatively high concentrations in testes and stomach tissues of dogs, but not rats, treated with I, a finding that may be related to species differences in toxicity observed with I in these species.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / metabolism*
  • Biotransformation
  • Carbon Radioisotopes
  • Chlorocebus aethiops
  • Dogs
  • Female
  • Gastric Mucosa / metabolism
  • Macaca mulatta
  • Male
  • Methylurea Compounds / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Saimiri
  • Species Specificity
  • Testis / metabolism
  • Tissue Distribution

Substances

  • Anti-Ulcer Agents
  • Carbon Radioisotopes
  • Methylurea Compounds
  • N-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)-N',N'-dimethylurea