Pharmacokinetics, metabolism, and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration

Biochem Pharmacol. 1997 Sep 15;54(6):657-68. doi: 10.1016/s0006-2952(97)00190-1.


The pharmacokinetics, tissue distribution and metabolism of CGP 69846A, a 20-mer phosphorothioate oligodeoxynucleotide targeted against the 3'-untranslated region of human c-raf-1 kinase mRNA, were investigated in vivo in rats after intravenous and subcutaneous administration. Intravenous disposition studies with [3H]CGP 69846A were supported with analysis by capillary gel electrophoresis and electrospray mass spectrometry. In combination, these techniques provide a detailed account of the pharmacokinetic and metabolic profile for this compound. The elimination of CGP 69846A after a single intravenous dose was studied over extended periods in mice using whole-body autoradiography and capillary gel electrophoresis. Subcutaneous administration to rats resulted in a significant bioavailability with peak plasma levels 4.5-fold lower than after intravenous dosing. This dose route resulted in low interanimal variability and only slightly greater metabolism of the oligonucleotide compared to the intravenous administration.

MeSH terms

  • Animals
  • Electrophoresis, Capillary
  • Female
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Liver / metabolism
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides, Antisense*
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / blood
  • Oligonucleotides, Antisense / pharmacokinetics*
  • Protein Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-raf
  • Rats
  • Rats, Wistar
  • Thionucleotides / administration & dosage
  • Thionucleotides / blood
  • Thionucleotides / pharmacokinetics*
  • Tissue Distribution
  • Tritium


  • Oligodeoxyribonucleotides, Antisense
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins
  • Thionucleotides
  • Tritium
  • ISIS 5132
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf