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

Purpose. The objective of this study was to determine the pharmacokinetics and safety for NX 1838 following injection into the vitreous humor of rhesu s monkeys. Methods, Plasma and vitreous humor pharmacokinetics were determined followi ng 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 determin ed following six biweekly bilateral injections of 0.25 or 0.50 mg/eye or fo llowing four biweekly bilateral injections of 0.10 mg per eye followed by t wo biweekly bilateral injections of 1.0 mg per eye. Results, Plasma and vitreous humor NX1838 concentrations were linearly rela ted to the dose administered. NX1838 was cleared intact from the vitreous h umor into the plasma with a half-lift of approximately 94 h, which was in a greement with the plasma terminal half-life. Vascular endothelial growth fa ctor (VEGF)-binding assays demonstrated that the NX1838 remaining in the vi treous humor after 28 days was fully active. No toxicological effects or an tibody responses were evident. Conclusions. The no observable effect level was greater than six biweekly b ilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. Thes e pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regime ns in human clinical trials.