PREDICTED BIOLOGIC ACTIVITY OF INTRAVITREAL BEVACIZUMAB

In Brief Purpose: To create a time- and dose-dependent mathematical model that compares the intravitreal vascular endothelial growth factor (VEGF) binding activity of bevacizumab with that of ranibizumab. Methods: Intravitreal half-lives and relative equimolar VEGF binding activities of bevacizumab and ranibizumab were incorporated into a first-order decay model. Time-dependent bevacizumab activities (relative to ranibizumab) for different initial doses (1.25 and 2.5 mg) and reinjection intervals (single, weekly, and every 3 days) were calculated and graphed. Results: Twenty-seven days to 38 days after a single bevacizumab (1.25 mg) injection, the intravitreal VEGF binding activity would be comparable with that of ranibizumab at 30 days. Bevacizumab (2.5 mg) injections would need to be performed every 3 days for 1 month to equal the peak activity after a ranibizumab injection. Discussion: On the basis of this mathematical model, intravitreal bevacizumab maintains significant VEGF binding activity for 4 weeks to 5 weeks. More frequent bevacizumab injections increase the average binding activity but not to that seen with a single ranibizumab injection. By constructing a mathematical model using established doses, half-life data, and relative activities, the expected intraocular biologic activity of bevacizumab is compared with that of ranibizumab. After an intravitreal injection, bevacizumab activity between 27 days and 38 days would be comparable with ranibizumab activity at 30 days.