Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys

Pharm Res. 2000 Dec;17(12):1503-10. doi: 10.1023/a:1007657109012.


Purpose: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys.

Methods: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharmacokinetics and toxicological properties of NX1838 were determined following six biweekly bilateral injections of 0.25 or 0.50 mg/eye or following four biweekly bilateral injections of 0.10 mg per eye followed by two biweekly bilateral injections of 1.0 mg per eye.

Results: Plasma and vitreous humor NX1838 concentrations were linearly related to the dose administered. NX1838 was cleared intact from the vitreous humor into the plasma with a half-life of approximately 94 h, which was in agreement with the plasma terminal half-life. Vascular endothelial growth factor (VEGF)-binding assays demonstrated that the NX1838 remaining in the vitreous humor after 28 days was fully active. No toxicological effects or antibody responses were evident.

Conclusions: The no observable effect level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Eating / drug effects
  • Electroretinography
  • Endothelial Growth Factors / antagonists & inhibitors*
  • Endothelial Growth Factors / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Injections
  • Lymphokines / antagonists & inhibitors*
  • Lymphokines / metabolism
  • Macaca mulatta
  • Male
  • Oligonucleotides / pharmacology*
  • Organ Size / drug effects
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Vitreous Body / metabolism
  • Vitreous Body / physiology*


  • Endothelial Growth Factors
  • Lymphokines
  • Oligonucleotides
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • NX1838