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H. Kim, M.R. Robinson, S.S. Lee, P.M. Bungay, R.J. Lutz, R.L. Dedrick, P. Yuan, K.G. Csaky; Compartmental Analysis of Rituxan Following an Intravitreal Injection . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5384.
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Purpose:Rituxan (Rituximab) is a monoclonal antibody directed against B cell–specific antigen CD20 approved for the treatment of Non–Hodgkin’s Lymphoma. We investigated the pharmacokinetics of Rituxan using a 2–compartment model in the rabbit eye to assess the feasibility of treating primary intraocular lymphoma. Methods: Intravitreal injectons of Rituxan 0.1 ml (1 mg) were performed in NZW rabbits and drug concentrations in the aqueous and vitreous humor were detected as previously reported (King BA et al. Invest Ophthalmol Vis. Sci. 2001; 42: S176). Concentration data in the aqueous and vitreous humor were regressed separately to a single exponential equation to determine the half–life of intravitreal injection of Rituxan. Two–compartment analysis was performed to determine the elimination pathways and to calculate transport coefficients of intraocular Rituxan. Results:The aqueous and vitreous humor drug levels at each time point were found to show linear correlation in the y–axis semi–log plot; Concentration = 49.6 × exp(–0.131×t) R2=0.83 in the aqueous. Concentration = 399 × exp(–0.147×t) R2=0.96 in the vitreous. The half–life of Rituxan (1 mg) following an intravitreal injection was calculated to be 4.7 days. In the compartmental analysis, the transport of Rituxan across the retina was found to be negligible. The experimental data were fitted into a two–compartment model and the mass transport coefficients of Rituxan from the vitreous to the aqueous humor (k1), and from the aqueous humor to outside of the eye (k2), were 0.15 and 5.12 [day–1], respectively. Conclusions:The transport of Rituxan from the rabbit eye following an intravitreal injection appears to be exclusively through the anterior chamber. Since the pathogenesis of primary intraocular lymphoma begins at the level of the retinal pigment epithelium, Rituxan injected into the vitreous will likely treat cells in the vitreous cavity and aqueous humor but is likely to be ineffective for treating subretinal infiltrates under an intact retina.
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