Disposition of 6-chloro-2-pyridylmethyl nitrate, a new anti-anginal compound, in rats and dogs

Xenobiotica. 1988 Mar;18(3):291-300. doi: 10.3109/00498258809041665.

Abstract

1. The absorption, distribution, metabolism and excretion of 6-chloro-2- pyridylmethyl nitrate, a new anti-anginal compound, were investigated in rats and dogs after intravenous and peroral administration of the 14C-labelled or unlabelled drug. 2. The half-lives of plasma levels for the alpha and beta phase and systemic availability were 6 min, 42 min and 26-50% respectively in rats, and 8 min, 66 min and 5% respectively in dogs. 3. Radioactivity was rapidly distributed in the tissues of rats, and recovered mainly in the 0-24 h urine (95% of dose within 24 h) with no excretion in the expired air. 4. Several metabolites were detected on t.l.c. of rat and dog urine, and four were identified as N-(chloro-2-pyridylcarbonyl)-glycine (M1, 56%), N-acetyl-S-(6- chloro-2-pyridylmethyl)-L-cysteine (M2, 29%), 6-chloro-2-pyridinecarboxylic acid (M3, 5%) and 6-chloro-2-pyridylmethyl. beta-D-glucuronate (M4, 7%). No unchanged drug was excreted.

MeSH terms

  • Angina Pectoris / drug therapy*
  • Animals
  • Bile / metabolism
  • Chromatography, High Pressure Liquid
  • Dogs
  • Drug Evaluation, Preclinical
  • Feces / analysis
  • Male
  • Pyridines / pharmacokinetics*
  • Rats
  • Species Specificity
  • Tissue Distribution

Substances

  • Pyridines
  • 6-chloro-2-pyridylmethyl nitrate