Sang Jun Park1, Yewon Choi2, Young Mi Na1, Hye Kyoung Hong1, Ji Yeon Park1, Kyu Hyung Park1, Jae Yong Chung2, Se Joon Woo1. 1. Department of Ophthalmology Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 2. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea.
Abstract
PURPOSE: We determined the intraocular pharmacokinetic properties of intravitreally injected aflibercept (Eylea) in a rabbit model. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).
PURPOSE: We determined the intraocular pharmacokinetic properties of intravitreally injected aflibercept (Eylea) in a rabbit model. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).
Authors: Kun Ding; Lucia Eaton; Diana Bowley; Matthew Rieser; Qing Chang; Maria C Harris; Anca Clabbers; Feng Dong; Jikui Shen; Sean F Hackett; Debra S Touw; Jacqueline Bixby; Suju Zhong; Lorenzo Benatuil; Sahana Bose; Christine Grinnell; Gregory M Preston; Ramesh Iyer; Ramkrishna Sadhukhan; Susan Marchie; Gary Overmeyer; Tariq Ghayur; Deborah A van Riet; Shibo Tang; Peter A Campochario; Jijie Gu Journal: MAbs Date: 2017 Feb/Mar Impact factor: 5.857