Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits.

Ranibizumab (Lucentis) is a humanized antigen-binding fragment designed to inhibit all isoforms and active degradation products of vascular endothelial growth factor A (VEGF-A); it is in clinical development for the treatment of neovascular age-related macular degeneration (AMD). This study evaluated its pharmacokinetics (PK) and retinal distribution in rabbits when administered ...
intravitreally (ITV).A total of 27 New Zealand white rabbits received a single bilateral ITV injection of ranibizumab 625 muicrog/eye (Group 1, n = 24) or I-labeled ranibizumab 625 microg/eye, 22.5 microCi/eye (Group 2, n = 3). Ranibizumab concentration was determined in the vitreous, aqueous humor, and serum up to 60 days postdose by enzyme-linked immunosorbent assay in Group 1. Group 2 eyes were microautoradiographed on days 1-4.Ranibizumab has a terminal half-life of 2.9 days in the ocular compartments. Systemic exposure was low, measuring less than 0.01% of vitreous exposure when comparing AUC0-t values. Microautoradiography analysis demonstrated that ranibizumab penetrated all retinal layers, reaching the choriocapillaris on days 1, 2, and 4.This study demonstrates that following ITV injection, ranibizumab has a vitreous half-life of 2.9 days with minimal systemic exposure. Ranibizumab rapidly penetrates through the retina to reach the choroid, supporting its clinical development for neovascular AMD.
Mesh Terms:
Angiogenesis Inhibitors, Animals, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Aqueous Humor, Autoradiography, Enzyme-Linked Immunosorbent Assay, Injections, Male, Rabbits, Retina, Tissue Distribution, Vascular Endothelial Growth Factor A, Vitreous Body
Retina (Philadelphia, Pa.)
Date: Nov. 30, 2007
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