Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD

RL Avery, AA Castellarin, NC Steinle… - British Journal of …, 2014 - bjo.bmj.com
RL Avery, AA Castellarin, NC Steinle, DS Dhoot, DJ Pieramici, R See, S Couvillion…
British Journal of Ophthalmology, 2014bjo.bmj.com
Background Data comparing systemic exposure and systemic vascular endothelial growth
factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following
intravitreal injection are lacking. Methods Fifty-six patients with wet age-related macular
degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or
aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after
the first and third injections. Results Following the first dose, systemic exposure to aflibercept …
Background
Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking.
Methods
Fifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections.
Results
Following the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) VEGF levels with ranibizumab were largely unchanged, with mean trough level of 14.4 pg/mL compared with baseline of 17 pg/mL.
Conclusions
There are notable differences in systemic pharmacokinetics and pharmacodynamics among anti-VEGF treatments after intravitreal administration. All three agents rapidly moved into the bloodstream, but ranibizumab very quickly cleared, whereas bevacizumab and aflibercept demonstrated greater systemic exposure and produced a marked reduction in plasma free VEGF.
Trial registration number
NCT02118831.
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