Long-Term Tolerability and Serum Concentration of Bevacizumab (Avastin) when Injected in Newborn Rabbit Eyes

Abstract

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.