Ranibizumab and Aflibercept: Intraocular Pharmacokinetics and Their Effects on Aqueous VEGF Level in Vitrectomized and Nonvitrectomized Macaque Eyes.

PURPOSE We evaluated the pharmacokinetics of intravitreally injected ranibizumab and aflibercept, and their effects on VEGF in the aqueous humor of vitrectomized and nonvitrectomized macaque eyes. METHODS Intravitreal ranibizumab (IVR; 0.5 mg/50 μL) or intravitreal aflibercept (IVA; 2 mg/50 μL) was injected into the previously vitrectomized right eyes of three macaques and nonvitrectomized right eyes of three macaques. The left eyes served as controls (nonvitrectomized, noninjected). Aqueous humor was obtained from both eyes just before injection and on days 1 and 3, and weeks 1 to 8 after IVR and IVA. The ranibizumab, aflibercept, and VEGF concentrations were measured using enzyme-linked immunosorbent assays. RESULTS The half-lives in aqueous humor of nonvitrectomized and vitrectomized eyes were, respectively, 2.3 and 1.4 days for ranibizumab, and 2.2 and 1.5 days for aflibercept. Concentration of VEGF was decreased below the limit of detection (LOD) by IVR for 3 weeks in nonvitrectomized eyes and 1 week in vitrectomized eyes, respectively, and by IVA for 6 weeks in nonvitrectomized eyes and 4 weeks in vitrectomized eyes, respectively. In the untreated control eyes, the ranibizumab and aflibercept concentrations were below the LOD, and the VEGF aqueous concentrations remained unchanged after IVR and decreased for 3 days after IVA. CONCLUSIONS Intravitreally injected ranibizumab and aflibercept have similar half-lives in aqueous humor and shorter half-lives in vitrectomized eyes. Compared to IVR, IVA suppresses VEGF level for a longer time period.