Intraocular Pharmacokinetics of 10-fold Intravitreal Ranibizumab Injection Dose in Rabbits

• Published in: Translational vision science & technology Vol. 9; no. 4; p. 7
• Main Authors: Kim, Hyeong Min, Park, Young Joo, Lee, Simin, Son, Joo Young, Hong, Hye Kyoung, Ham, Min Hee, Jin, Xuanyou, Chung, Jae Yong, Park, Kyu Hyung, Park, Ki Dong, Woo, Se Joon
• Format: Journal Article
• Language: English
• Published: United States The Association for Research in Vision and Ophthalmology 01.03.2020
• Subjects: Angiogenesis Inhibitors - therapeutic use; Animals; Aqueous Humor; Intravitreal Injections; Rabbits; Ranibizumab; Vitreous Body; pharmacokinetics; intravitreal; concentration; efficacy; ranibizumab
• ISSN: 2164-2591; 2164-2591
• DOI: 10.1167/tvst.9.4.7

To investigate intraocular pharmacokinetics of 10-fold dose of intravitreally injected ranibizumab compared with the conventional dose in an experimental model. Ranibizumab 30 µL at 10 mg/mL (conventional) and 100 mg/mL (10-fold) doses was injected separately into each eye of 28 rabbits. Ranibizumab concentrations in the aqueous humor, vitreous, and retina were estimated at each time period after injection, using enzyme-linked immunosorbent assay. The pharmacokinetic properties of ranibizumab were determined using a one-compartment model in all three ocular tissues. The time-concentration profile and predictive trends were plotted to determine drug efficacy in the retina. Maximum concentrations after conventional and 10-fold dosing were observed in the retina at 1 and 4 days after injection, respectively. The half-life of ranibizumab after conventional and 10-fold dosing did not differ in the anterior chamber and vitreous, whereas the half-life was prolonged approximately twice with the 10-fold dose in the retina (36.74 h vs. 76.85 h) and serum (91.93 h vs. 179.01 h). Similarly, the estimated time for ranibizumab concentration in the retina over 27 ng/mL (minimum effective concentration of ranibizumab) was prolonged approximately twice with the 10-fold dose (1315 h [55 days] vs. 2393 h [100 days]). No adverse effects were observed in either group. The retinal half-life and concentration of ranibizumab in rabbit eyes were increased approximately twice after a 10-fold dose compared with the conventional dose. This finding indicates a possibility to lengthen the injection interval to improve the efficacy of ranibizumab in human eyes. Our results highlight the potential for clinical application of a high-dose (10-fold) of anti-VEGF agents to prolong the intravitreal injection intervals, simultaneously improving the drug efficacy.