Abstract
Purpose :
To investigate the pharmacokinetics (PK) of intravitreal aflibercept injection (IAI) in eyes with neovascular age related macular degeneration (NV AMD).
Methods :
Five eyes from 5 patients with new onset NV AMD were enrolled in this study. Subjects were followed for a 28-day period and had 6 study visits (baseline, days 1, 3, 7, 14, and 28). All study eyes were treatment naïve and received a single dose of 2mg IAI at baseline. Anterior chamber paracentesis to collect aqueous humor (AH) was performed at all study visits[SR1] . In addition, plasma blood samples were also obtained. Free aflibercept concentrations in AH and plasma were measured using enzyme-linked immunosorbent assays (ELISA). Pharmacokinetics of free aflibercept in both AH and plasma was also evaluated. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were also obtained at every visit.
Results :
Following a single dose of 2mg IAI, the mean Cmax (peak concentrations) of free aflibercept in AH was 111 mg/L (range: 35 – 222 mg/L), and half-life of ~9 days was determined. The mean AUCinf (area under the concentration-time curve extrapolated to infinity) in AH was 846 mg*day/L. The mean Cmax of free aflibercept in plasma was 0.03 mg/L based on measurements from 3 patients (2 out of 5 patients had no detectable concentrations). Drug was undetectable one week post dosing in plasma in all patients. Additional PK parameters in plasma were not calculated because of the low concentrations of free aflibercept in the plasma.
Conclusions :
A half-life of ~9 days for aflibercept was determined based on AH samples from 5 eyes of patients with NV AMD. Free aflibercept had ~1000-fold greater exposure in eyes as compared to plasma concentrations. The plasma exposures of free aflibercept were not substantial with low systemic concentrations following a single dose which are consistent with previous studies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.