title: Ranibizumab and Aflibercept: Intraocular Pharmacokinetics and Their Effects on Aqueous VEGF Level in Vitrectomized and Nonvitrectomized Macaque Eyes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology Shiga University of Medical Science, Otsu, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Niwa
authors.affiliation: Department of Ophthalmology Shiga University of Medical Science, Otsu, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kakinoki
authors.affiliation: Department of Ophthalmology Shiga University of Medical Science, Otsu, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Department of Ophthalmology Shiga University of Medical Science, Otsu, Japan 2Key Laboratory of Harbin Medical University Eye Center, Eye Hospital, First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xiying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology Shiga University of Medical Science, Otsu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ohji
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058449:Intravitreal Injections; D008251:Macaca; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D000069579:Ranibizumab / Q000008:administration & dosage / Q000493:pharmacokinetics*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014821:Vitrectomy; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab