The introduction of anti-VEGF treatment has changed the paradigm of standard treatment for and improved visual prognosis of VEGF-related ocular diseases, such as exudative age-related macular degeneration (AMD), diabetic macular edema, and retinal vein occlusion. Intravitreal ranibizumab (Lucentis; Genentech, Inc., San Francisco, CA, USA) has been used widely as a first-line treatment for these vision-threatening conditions, along with the off-label use of intravitreal bevacizumab (Avastin; Genentech, Inc.). Recently, aflibercept (VEGF Trap-Eye, Eylea; Regeneron, Inc., Tarrytown, NY, USA and Bayer Healthcare Pharmaceuticals, Berlin, Germany) was approved for therapeutic use and has since been used widely. Aflibercept has greater binding affinity to VEGF than does ranibizumab or bevacizumab, which indicates longer duration of action for aflibercept in the eyes.
1–3 However, unlike that for ranibizumab and bevacizumab, data for the intraocular pharmacokinetics (PK) of aflibercept are scarce. A rabbit model–based PK study reported intravitreal PK properties of intravitreally administrated I-124–labeled aflibercept by the use of positron emission tomography/computed tomography (PET/CT) imaging; the intravitreal half-life of I-124–aflibercept was 4.58 days, which was similar to the manufacturer data of 4.79 days.
2,4 Meanwhile, another PK study using a conventional immunoassay-based macaques model showed aqueous humor PK properties of intravitreally administrated aflibercept in comparison with ranibizumab; intravitreally administrated aflibercept and ranibizumab have similar half-lives in aqueous humor (2.2 and 2.3 days, respectively).
5 However, to our knowledge, no study has addressed detailed, comparable intraocular PK properties of aflibercept by the use of a conventional immunoassay-based rabbit model as did the previous PK studies for ranibizumab and bevacizumab.
6–12 This resulted in our recent study investigating the detailed intraocular PK properties of intravitreally administrated VEGF-Trap, a prototype of VEGF Trap-Eye, by the use of a conventional immunoassay-based rabbit model.
3 However, although the sequences of VEGF-Trap and VEGF Trap-Eye are similar and show differences in only 5.3% (25 of 476) of the amino acids, these differences might result in differences in their intraocular PK properties.
1,3 Moreover, the commercially available VEGF Trap-Eye, Eylea, (which is widely used in clinical practice) passes through several manufacturing processes, which also might affect its intraocular PK properties. Hence, in this study, we investigated the intraocular PK properties of aflibercept (Eylea) in the same experimental setting described in our previous PK studies for bevacizumab, ranibizumab, and VEGF-Trap to provide comparable PK data of aflibercept with that of bevacizumab, ranibizumab, and VEGF-Trap.
3,6,7