title: The pharmacokinetics of rituximab following an intravitreal injection.
abstract: Rituximab is a monoclonal antibody directed against the CD20 B-cell antigen and is approved for the treatment of B-cell lymphoma. We investigated the pharmacokinetics of rituximab following intravitreal administration to assess the feasibility of treating primary intraocular lymphoma. Intravitreal injections of rituximab 0.1 ml (1 mg) were performed in rabbits. Drug concentrations in the aqueous and vitreous humor were measured at intervals from 2 to 17 days after administration. The half-life of the total amount of rituximab in the two compartments was calculated to be 4.7 days. The aqueous and vitreous humor drug levels decayed in parallel maintaining an average ratio of approximately seven. Fitting the data to a two-compartment model yielded a clearance from the aqueous humor of 1.2 microl/min. The clearance was less than the reported rate of aqueous humor outflow indicating that elimination by this route could have been sufficient to account for the disappearance of the drug from the eye. The duration of time over which sustained levels of rituximab were achieved suggest that intravitreal administration warrants further investigation as an approach to treating vitreous and anterior chamber infiltrates in patients with primary intraocular lymphoma.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1863, USA.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bungay
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lutz
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dedrick
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Jay
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Grillo-Lopez
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D001082:Aqueous Humor / Q000378:metabolism*; D005134:Eye Neoplasms / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006207:Half-Life; D007267:Injections; D016393:Lymphoma, B-Cell / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011817:Rabbits; D000069283:Rituximab; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab