Pharmacokinetics of intravitreal ranibizumab (Lucentis)

Purpose: To describe the pharmacokinetics of 0.5 mg of intravitreal ranibizumab (Lucentis) and to compare it with that of 1.25 mg of intravitreal bevacizumab (Avastin), using the same rabbit model. Design: Experimental animal study. Participants: Twenty-eight Dutch-belted rabbits. Methods: One eye of each of 20 rabbits was injected with 0.5 mg of intravitreal ranibizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Ranibizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. A further 8 rabbits were used to measure serum and fellow ranibizumab at additional time points of 3 and 8 hours. Main Outcome Measures: Ranibizumab concentrations in the aqueous, vitreous, and serum. Results: Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 mu g/ml ranibizumab were maintained in the vitreous humor for 29 days. Ranibizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 17.9 mu g/ml, 3 days after drug administration. Elimination of ranibizumab from the aqueous humor paralleled that found in the vitreous humor, with a half-life value of 2.84 days. No ranibizumab was detected in the serum or the fellow eye. Conclusion: In the rabbit, the vitreous half-life of 0.5-mg intravitreal ranibizumab is 2.88 days, shorter than the half-life of 1.25-mg intravitreal bevacizumab of 4.32 days. No ranibizumab was detected in the serum or the fellow uninjected eye; whereas small amounts of intravitreal bevacizumab have been detected in the serum and fellow uninjected eye.