Long-term tolerability and serum concentration of bevacizumab (avastin) when injected in newborn rabbit eyes.
PURPOSE. To test the long-term effects and systemic exposure level after single or multiple bevacizumab (Avastin) intravitreal injections in newborn rabbit eyes. METHODS. Four groups of newborn New Zealand rabbits received a single intravitreal bevacizumab injection at a concentration of 1.25 mg/0.05 mL at the ages of 2 (group 1), 4 (group 2), 6 (group 3), and 12 (group 5) weeks. The other group of rabbits (group 4) received three consecutive injections of bevacizumab at a concentration of 1.25 mg/0.05 mL at weeks 2, 6, and 10. Eight days after injection, the serum concentration of bevacizumab was determined in groups 1, 2, 3, and 5. Morphologic and functional changes were evaluated 12 months after bevacizumab injection. RESULTS. Twelve months after either single or multiple intravitreal injections of bevacizumab, newborn rabbit eyes showed no significant differences compared with control eyes on examination with funduscopy, histopathology, or electroretinogram. The serum concentrations when the injections were performed at the ages of 2 (19.4 +/- 8.1 microg/mL) and 4 (10.2 +/- 2.3 microg/mL) weeks were significantly higher than the serum level detected when the injection was performed at 12 weeks of age (2.8 +/- 1.2 microg/mL, P = 0.02 and P = 0.024, respectively). CONCLUSIONS. After 1 year, single and three consecutive intravitreal injections of 1.25 mg bevacizumab in newborn rabbit eyes are well tolerated. Systemic exposure is higher when the injection is performed at an early age.
Wu
Wei-Chi
WC
Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. weichi666@gmail.com
Lai
Chi-Chun
CC
Chen
Kuan-Jen
KJ
Chen
Tun-Lu
TL
Wang
Nan-Kai
NK
Hwang
Yih-Shiou
YS
Yeung
Ling
L
Li
Lien-Min
LM
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001682:Biological Availability; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007267:Injections; D016900:Neurofilament Proteins / Q000378:metabolism; D055355:Opsins / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D055355:Opsins; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab