Intraocular Pharmacokinetics of Intravitreal Aflibercept (Eylea) in a Rabbit Model.
We determined the intraocular pharmacokinetic properties of intravitreally injected aflibercept (Eylea) in a rabbit model.



Aflibercept was injected intravitreally in 21 eyes from New Zealand White rabbits. The eyes were enucleated 1, 24, 48, 120, 216, 360, and 720 hours (1, 2, 5, 9, 15, and 30 days, respectively) after injection and immediately frozen at -80°C. The concentrations of aflibercept in the vitreous, aqueous humor, and retina/choroid were determined by performing an indirect enzyme-linked immunosorbent assay, and analyzed to understand the pharmacokinetic properties of the drug.



The maximum concentration of aflibercept was observed 1, 48 (2 days), and 24 (1 day) hours after intravitreal administration in the vitreous, aqueous humor, and retina/choroid, respectively. The one-compartment model was selected as the final model for all three ocular tissues. In the vitreous, aqueous humor, and retina/choroid, the estimated half-lives of aflibercept were 94.1, 48.0, and 58.2 hours, and the estimated mean residence times (MRTs) were 135.8, 69.2, and 84.0 hours, respectively. The area under curve from time 0 to the end point (AUClast) was 135,810.6 hours × μg/mL for the vitreous, 13,889.7 hours × μg/mL for the aqueous humor, and 2453.1 hours × μg/g for the retina/choroid.



In rabbits, the vitreous half-life of aflibercept is 94.1 hours (3.92 days). This is shorter than that of bevacizumab (6.99 days), and longer than that of ranibizumab (2.51 days) and VEGF-Trap (3.63 days).
Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Sang Jun
SJ
Park
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.
Yewon
Y
Choi
Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Young Mi
YM
Na
Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Hye Kyoung
HK
Hong
Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Ji Yeon
JY
Park
Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Kyu Hyung
KH
Park
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.
Jae Yong
JY
Chung
Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Se Joon
SJ
Woo
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002829:Choroid / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058449:Intravitreal Injections; D011817:Rabbits; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor