The DOI matches its Crossref record.
Preclinical Pharmacokinetics of Ranibizumab (rhuFabV2) after a Single Intravitreal Administration
Abstract
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 microg/eye; n = 6/group) or a single IV dose (1000 or 4000 microg/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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FERRARA, N., DAMICO, L., SHAMS, N., LOWMAN, H., & KIM, R. (2006) · Retina · doi:10.1097/01.iae.0000242842.14624.e7 · Cited by 849
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A comprehensive insight on ocular pharmacokinetics
Agrahari, V., Mandal, A., Agrahari, V., Trinh, H. M., Joseph, M., Ray, A., Hadji, H., Mitra, R., Pal, D., & Mitra, A. K. (2016) · Drug Delivery and Translational Research · doi:10.1007/s13346-016-0339-2 · Cited by 462
Wu, L., Martínez-Castellanos, M. A., Quiroz-Mercado, H., Arevalo, J. F., Berrocal, M. H., Farah, M. E., Maia, M., Roca, J. A., Rodriguez, F. J., & for the Pan American Collaborative Retina Group (PACORES) (2007) · Graefe's Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-007-0660-z · Cited by 456
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Obeid, A., Su, D., Patel, S. N., Uhr, J. H., Borkar, D., Gao, X., Fineman, M. S., Regillo, C. D., Maguire, J. I., Garg, S. J., et al. (2019) · Ophthalmology · doi:10.1016/j.ophtha.2018.07.027 · Cited by 180
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Maguire, M. G., Daniel, E., Shah, A. R., Grunwald, J. E., Hagstrom, S. A., Avery, R. L., Huang, J., Martin, R. W., Roth, D. B., Castellarin, A. A., et al. (2013) · Ophthalmology · doi:10.1016/j.ophtha.2013.03.017 · Cited by 93
Use of rabbit eyes in pharmacokinetic studies of intraocular drugs
Ahn, S. J., Hong, H. K., Na, Y. M., Park, S. J., Ahn, J., Oh, J., Chung, J. Y., Park, K. H., & Woo, S. J. (2016) · Journal of Visualized Experiments · doi:10.3791/53878 · Cited by 60
Bussing, D., Li, Z., Li, Y., Chang, H.-P., Chang, H.-Y., Guo, L., Verma, A., & Shah, D. K. (2021) · The AAPS Journal · doi:10.1208/s12248-021-00647-0 · Cited by 16
Metadata
- Authors
- Gaudreault, J., Fei, D., Rusit, J., Suboc, P., & Shiu, V.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2005-02-01
- Volume
- 46
- Issue
- 2
- Pages
- 726
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2091407629
- Cited by
- 501
- References
- 0
- FWCI
- 28.22
- Type
- journal article
- Language
- en
- Open access
- closed
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