title: Intraocular Pharmacokinetics of Aflibercept and Vascular Endothelial Growth Factor-A.
abstract: OBJECTIVE
  To determine intraocular pharmacokinetics of aflibercept and VEGF-A in patients with neovascular age-related macular degeneration (nAMD) during a treatment period of 6 months.
  
  
  METHODS
  Seven nonvitrectomized patients diagnosed with macular edema secondary to nAMD undergoing intravitreal injections (IVI) of aflibercept. Patients were treatment naïve at least for the last 2 months and received intravitreal injection of 2 mg aflibercept for the first time. Aqueous humor samples were obtained prior to each injection procedure during a 6-month period: three times monthly, then bimonthly. Over all 35 samples were analyzed with ELISA for unbound VEGF-A and a self-developed assay for unbound aflibercept.
  
  
  RESULTS
  In all cases, wet AMD was inactive after IVI. Unbound aflibercept could be detected in all samples. Initial mean concentration of aflibercept was 305.4 ± 43.8 μg/mL and remained stable after the first injection with 0.8 ± 0.5 μg/mL. Initial mean level of unbound VEGF-A was 190.7 ± 26.9 pg/mL. A significant decrease of the concentration to 92.6 ± 10.2 pg/mL (P < 0.05, Wilcoxon rank sum test) after the first injection was observed. This level remained stable during further treatment.
  
  
  CONCLUSIONS
  Levels of unbound aflibercept and unbound VEGF-A remained stable after every month and every second month of IVI. The findings of these small case series support suggestions that treatment intervals with bimonthly IVI of aflibercept are sufficient due to a detectable remaining biologic active concentration of aflibercept.
authors: University Hospital Heidelberg, Department of Ophthalmology, Heidelberg, Germany.
authors: Nil
authors: N
authors: Celik
authors: University Hospital Heidelberg, Department of Ophthalmology, Heidelberg, Germany.
authors: Alexander
authors: A
authors: Scheuerle
authors: University Hospital Heidelberg, Department of Ophthalmology, Heidelberg, Germany.
authors: Gerd U
authors: GU
authors: Auffarth
authors: University of Heidelberg, Department of Pathology, Heidelberg, Germany.
authors: Jürgen
authors: J
authors: Kopitz
authors: University Hospital Heidelberg, Department of Ophthalmology, Heidelberg, Germany 3Department of Ophthalmology, Klinikum Wiesbaden (HSK), Wiesbaden, Germany.
authors: Stefan
authors: S
authors: Dithmar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014792:Visual Acuity
chemical_list: D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor