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Brandon G. Busbee, Wendy Yee Murahashi, Zhenling Yao, Yi Zhang; Ranibizumab Pharmacokinetics in Retinal Vein Occlusion. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4874.
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Characterize ranibizumab pharmacokinetics (PK) in patients with retinal vein occlusion (RVO) and identify patient characteristics and disease-specific factors that may affect PK and necessitate dose adjustment.
Ranibizumab concentration was measured in 1,647 serum samples from 520 patients with macular edema following RVO treated with monthly intraocular injections of 0.3 mg or 0.5 mg ranibizumab. A one-compartment PK model with first-order absorption and elimination rate constants was fit to the data. Population PK parameters and interindividual variability were estimated. Patient baseline characteristics (RVO subtype and duration, creatinine clearance [CrCL], intraocular pressure, area of nonperfusion, visual acuity, central foveal thickness) were evaluated for potential effects on systemic PK. A mixed-effect modeling approach was adopted using NONMEM VI software. General diagnostic plots and a visual predictive check were used to evaluate model performance.
The model well described the serum concentration data, and parameters were estimated with acceptable precision. The rate of ranibizumab elimination was limited by the rate of absorption from the vitreous. Patient baseline characteristics did not have a significant effect on systemic exposure or drug elimination from the vitreous. CrCL was estimated to be a statistically significant source of variability on clearance. However, further analysis showed that this variability would have minimal clinical impact on efficacy and safety.
Disease-related patient baseline characteristics did not have a clinically meaningful impact on ranibizumab disposition. Dose adjustment is not recommended when considering ranibizumab for treatment of RVO.
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