Detection and plasma pharmacokinetics of an anti-vascular endothelial growth factor oligonucleotide-aptamer (NX1838) in rhesus monkeys

J Chromatogr B Biomed Sci Appl. 1999 Sep 10;732(1):203-12. doi: 10.1016/s0378-4347(99)00285-6.

Abstract

Aptamers are oligonucleotide ligands selected, in vitro, to bind a specified target protein. The first aptamer to reach human clinical testing is NX1838, a polyethylene glycol conjugated aptamer that inhibits vascular endothelial growth factor. This paper describes the validation of a high-performance liquid chromatographic anion-exchange method for the determination of NX1838 in plasma. Measurements of intact NX1838 had a coefficient of variation of less than 8% and an accuracy between 107% and 115%. The assay was utilized to determine NX1838 plasma pharmacokinetics in rhesus monkeys following a single 1 mg/kg intravenous or subcutaneous dose. Following intravenous administration, the maximum achieved plasma concentration was 25.5 microg/ml with a terminal half-life of 9.3 h and clearance rate of 6.2 ml/h. After subcutaneous administration, the fraction of the dose absorbed into the plasma compartment was 0.78 with a time to peak concentration (4.9 microg/ml) of 8 to 12 h.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Endothelial Growth Factors / antagonists & inhibitors
  • Endothelial Growth Factors / metabolism*
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Lymphokines / antagonists & inhibitors
  • Lymphokines / metabolism*
  • Macaca mulatta
  • Oligonucleotides / blood*
  • Oligonucleotides / metabolism
  • Oligonucleotides / pharmacokinetics
  • Quality Control
  • Reproducibility of Results
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Oligonucleotides
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors