Disposition and metabolism of prinomide in laboratory animals

The disposition and metabolism of prinomide, the 1:1 triethanolamine salt of 1-methyl-β-oxo-α (phenylcarbamoyl)-2-pyrrole-propionitrile (CGS 10787B), have been investigated in a number of animal species after single and multiple oral dosing with 14C-labeled and unlabeled drug. Following single oral doses of 25 to 50 mg/kg of 14C-prinomide to mice, rats, hamsters, dogs, cynomolgus monkeys and baboons, radioactivity was excreted primarily in urine, in the form of metabolites. However, in the mouse and monkey, fecal excretion was also significant. In the cynomolgus monkey, a radioactive dose of drug administered following multiple doses of unlabeled drug gave rise to peak plasma concentrations of radioactivity within 1 to 6 hr. Intact prinomide accounted for approximately 69% of this radioactivity. The terminal plasma half-life of the drug was 24 to 41 hr. Studies in rats with 14C-prinomide indicated that radioactivity was distributed rapidly to all tissues, with the highest levels being observed in blood and well perfused organs and tissues. The lowest levels were detected in adipose tissue, eyes, and brain. The metabolism of prinomide was qualitatively similar in all species investigated