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

@entity1 @entity1020 @entity7
BACKGROUND: Data comparing systemic exposure and systemic @entity7 ( @entity7 ) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking. METHODS: Fifty-six @entity1 with wet age-related @entity1020 received intravitreal ranibizumab (0.5   mg), bevacizumab (1.25   mg), or aflibercept (2.0   mg). Serum pharmacokinetics and plasma free @entity7 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 @entity7 , with mean levels below lower limit of quantitation (10   pg/mL) as early as 3   h postdose until >= 7   days postdose. Mean free (unbound) @entity7 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- @entity7 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 @entity7 . TRIAL REGISTRATION NUMBER: NCT02118831.
