Assessement of the pharmacokinetics, tissue distribution and excretion studies of a novel antiplatelet agent S007-867, following administration to rats

Drug Test Anal. 2016 Jul;8(7):723-9. doi: 10.1002/dta.1811. Epub 2015 Jul 3.

Abstract

S007-867 is a promising novel antiplatelet agent with better efficacy and lesser bleeding risk than existing agents. The present study investigated the absorption, tissue distribution, and excretion of S007-867 in rat model for further advancement of the molecule. A simple and robust ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) bioanalytical method was used to determine S007-867 in various matrices. Following oral administration, the compound was quickly dispersed in the various tissues and peak concentration levels were achieved within 0.5-1 h. Overall, exposure of drug, i.e., AUC in different tissues was found in the order of small intestine > liver > heart > spleen > lungs > kidney > brain. The total recoveries of the S007-867 within 96 h were 3.36% in urine and faeces. This might be due to a first-pass effect by the liver and intestine as most of the drug was eliminated in metabolite form. These findings provide a crucial information about further development of S007-867 as antithrombotic agent. Copyright © 2015 John Wiley & Sons, Ltd.

Keywords: absorption; excretion; metabolism; pharmacokinetics; rat; tissue distribution.

MeSH terms

  • Administration, Oral
  • Animals
  • Chromatography, High Pressure Liquid / economics
  • Chromatography, High Pressure Liquid / methods*
  • Feces / chemistry
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Aggregation Inhibitors / urine
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / economics
  • Tandem Mass Spectrometry / methods*
  • Tissue Distribution

Substances

  • Platelet Aggregation Inhibitors