Purpose: To investigate the ocular pharmacokinetic properties of intravitreally injected aflibercept in rabbits after using brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops. Methods: The right eye of 5 rabbits was topically administered 30 μL of brinzolamide and timolol maleate eye drops twice a day (q12h). The 2 eyes of each rabbit were injected with 1.0 mg (0.025 cc) of aflibercept on the 2nd day after instilling the eye drops. The intraocular pressure of the rabbits was measured before injection and sampling. The aqueous humor was drawn at 1, 3, 7, 14, 21, and 28 days. Aflibercept concentrations in aqueous humor and vitreous humor (28 days) were measured by enzyme-linked immunosorbent assay. Results: The aflibercept aqueous concentrations in the right eye at days 7, 14, 21, and 28 after injection were all significantly higher than those in the left eye (P > 0.05, n = 5). The peak aqueous concentrations of aflibercept in right eyes (49.5 μg/mL) and left eyes (50.9 μg/mL) were both observed at 1 day after injection. The elimination half-life of aflibercept in the aqueous humor of the right eye (4.70 days) was 1 day longer than that of the left eye (3.65 days). The average percentage of residual aflibercept in the vitreous humor of the right eye (3.35%) was also significantly higher than that of the left eye (0.63%). Conclusions: Brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops can significantly extend the ocular residence time of intravitreally injected aflibercept.
Keywords: aflibercept; anti-VEGF agents; aqueous humor secretion; brinzolamide and timolol; ocular pharmacokinetics.