title: Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model.
abstract: OBJECTIVE
  To determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model.
  
  
  METHODS
  VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately frozen at -80 °C. Concentration of VEGF-Trap in vitreous, aqueous humor, and retina/choroid was determined using an indirect enzyme-linked immunosorbent assay and analyzed to obtain pharmacokinetic properties.
  
  
  RESULTS
  Maximum concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one-compartment model of distribution was selected as the final model for all tissues studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9% of vitreous exposure, respectively.
  
  
  CONCLUSIONS
  The vitreous half-life of VEGF-Trap is 3.63 days. This is shorter than that of bevacizumab (6.99 days) and longer than that of ranibizumab (2.51 days), as shown in studies using the same experimental settings. The concentration of VEGF-Trap peaked at 1 h after injections in all eye tissues studied.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: H K
authors.initials: HK
authors.lastname: Hong
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Park
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
authors.forename: J-E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Woo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D019540:Area Under Curve; D002829:Choroid / Q000378:metabolism*; D006207:Half-Life; D058449:Intravitreal Injections; D023421:Models, Animal; D011817:Rabbits; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012160:Retina / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor