Metabolism of N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6- tetrahydrophthalimide (S-23121) in the rat. II. Absorption, disposition, excretion and biotransformation

Xenobiotica. 1993 Oct;23(10):1075-84. doi: 10.3109/00498259309059423.

Abstract

1. To examine the metabolic fate of N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6- tetrahydrophthalimide (S-23121), rats were given a single oral dose of [phenyl-14C]S-23121 at 1 or 250 mg/kg. 2. The radiocarbon was almost completely eliminated from the rat within 7 days after administration for both dose groups. Faecal 14C-excretion was major (71-86% of the dose) and urinary 14C-excretion was minor (18-30%). 3. 14C-tissue residues on the seventh day after administration were generally very low. Peak 14C-concentrations in the kidney and liver occurred 4 h after administration and decreased rapidly thereafter. Amounts (percentage of dose) of the parent compound in faeces were 13-26% for low dose, and 22-35% for high dose. 4. The major metabolites in faeces were sulphonic acid conjugates (13-20% of the administered dose), formed by incorporation of a sulphonic acid group into the double bond of the tetrahydrophthalimide. The major metabolites in urine were sulphates and glucuronides of 4-chloro-2-fluoro-5-hydroxyaniline, amounting to 5-7 and 2-3% of the administered dose, respectively. Sulphonic acid conjugates were not detected in urine, blood, kidney or liver.

MeSH terms

  • Animals
  • Chromatography, Thin Layer
  • Feces
  • Female
  • Herbicides / administration & dosage
  • Herbicides / metabolism*
  • Herbicides / pharmacokinetics
  • Intestinal Absorption
  • Male
  • Phthalimides / administration & dosage
  • Phthalimides / metabolism*
  • Phthalimides / pharmacokinetics
  • Radiochemistry
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Herbicides
  • Phthalimides
  • S 23121