Predicted biological activity of intravitreal VEGF Trap.
OBJECTIVE
To compare the intravitreal binding activity of VEGF Trap with that of ranibizumab against vascular endothelial growth factor (VEGF) using a time-dependent and dose-dependent mathematical model.


METHODS
Intravitreal half-lives and relative equimolar VEGF-binding activities of VEGF Trap and ranibizumab were incorporated into a first-order decay model. Time-dependent VEGF Trap activities (relative to ranibizumab) for different initial doses (0.5, 1.15, 2 and 4 mg) were calculated and plotted.


RESULTS
Seventy-nine days after a single VEGF Trap (1.15 mg) injection, the intravitreal VEGF-binding activity would be comparable to ranibizumab at 30 days. After injection of 0.5, 2 and 4 mg VEGF Trap, the intravitreal VEGF-binding activities (comparable to ranibizumab at 30 days) would occur at 73, 83 and 87 days, respectively


CONCLUSIONS
On the basis of this mathematical model, VEGF Trap maintains significant intravitreal VEGF-binding activity for 10-12 weeks after a single injection.
Stewart
M W
MW
Mayo Clinic College of Medicine, Jacksonville, Florida, USA. stewart.michael@mayo.edu
Rosenfeld
P J
PJ
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007267:Injections; D008268:Macular Degeneration / Q000188:drug therapy*; D023421:Models, Animal; D011817:Rabbits; D000069579:Ranibizumab; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D042461:Vascular Endothelial Growth Factor A / Q000493:pharmacokinetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000069579:Ranibizumab