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Preclinical Pharmacokinetics of Ranibizumab (rhuFabV2) after a Single Intravitreal Administration

¹From the Departments of Pharmacokinetic and Pharmacodynamic Sciences, ²Bioanalytical Research and Development, and ³BioAnalytical Assays, Genentech, Inc., South San Francisco, California.

PURPOSE. Ranibizumab (rhuFab V2; Lucentis, Genentech, South San Francisco, CA) is a humanized monoclonal antibody fragment designed to bind all forms of VEGF, thereby blocking vessel permeability and angiogenesis in neovascular age-related macular degeneration. This study evaluated the pharmacokinetic (PK) and serum bioavailability of ranibizumab after a single intravitreal (ITV) or intravenous (IV) dose in cynomolgus monkeys.

METHODS. Monkeys received ranibizumab as either a bilateral ITV dose (500 or 2000 µg/eye; n = 6/group) or a single IV dose (1000 or 4000 µg/animal; n = 4/group). After ITV administration, ranibizumab concentrations were measured in several ocular compartments and in serum for 10 days and, after IV administration, for 48 hours. Pharmacokinetic parameters were estimated by compartmental and noncompartmental methods.

RESULTS. Ranibizumab cleared in parallel from all ocular compartments, with a terminal half-life of approximately 3 days. It distributed rapidly to the retina (6–24 hours), and concentrations were approximately one third that in the vitreous. After ITV injection, bioavailability (F) was 50% to 60%. Serum concentrations were very low, reflecting wider distribution and faster clearance when ranibizumab reached the serum. After IV administration, the terminal half-life was approximately 0.5 day.

CONCLUSIONS. This study demonstrates that ranibizumab has a PK profile that is favorable for its clinical use in treating neovascular AMD by monthly ITV injection.

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