Intraocular pharmacokinetics of ranibizumab in vitrectomized versus nonvitrectomized eyes

• Published in: Investigative ophthalmology & visual science 2014-01, Vol.55 (1), p.567-573
• Main Authors: Ahn, Seong Joon, Ahn, Jeeyun, Park, Sunyoung, Kim, Hyuncheol, Hwang, Duck Jin, Park, Ji Hyun, Park, Ji Yeon, Chung, Jae Yong, Park, Kyu Hyung, Woo, Se Joon
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - pharmacokinetics; Aqueous Humor - metabolism; Disease Models, Animal; Immunoassay; Intravitreal Injections; Macular Degeneration - drug therapy; Macular Degeneration - metabolism; Macular Degeneration - surgery; Rabbits; Ranibizumab; Retina - metabolism; Vitrectomy; Vitreous Body - metabolism
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.13-13054

To analyze the intraocular pharmacokinetic properties of intravitreally injected ranibizumab in vitrectomized and nonvitrectomized rabbit eyes. A procedure consisting of 25-gauge pars plana vitrectomy without lensectomy and posterior vitreous detachment was performed in 18 rabbit eyes, and 18 nonvitrectomized rabbit eyes served as controls. Ranibizumab (0.25 mg/0.025 mL) was intravitreally injected in all the vitrectomized and nonvitrectomized eyes. The eyes were enucleated at 1 hour or 1, 2, 5, 14, or 30 days after the intravitreal injections and frozen at -80°C. Ranibizumab concentrations in the vitreous, aqueous humor, and retina were determined using indirect enzyme-linked immunosorbent assay. Vitreous clearance of ranibizumab showed a 2-phase elimination. The vitrectomized and nonvitrectomized eyes showed comparable rates of vitreous clearance of ranibizumab. The vitreous half-life of ranibizumab for up to 14 days was 2.51 and 2.75 days in vitrectomized and nonvitrectomized eyes, respectively. Throughout the 30-day period after intravitreal injection, there were no statistically significant differences between the concentrations of ranibizumab in the vitreous, aqueous humor, and retina of vitrectomized eyes and those in nonvitrectomized eyes. Concentrations of ranibizumab in the vitreous peaked 1 hour after injection, with a mean concentration of 118.01 and 91.61 μg/mL in vitrectomized and nonvitrectomized eyes, respectively. The elimination rate constant of intravitreal ranibizumab in 1-phase analyses showed only a 9% increase in vitrectomized eyes compared to nonvitrectomized eyes. Overall intraocular pharmacokinetic properties of ranibizumab in vitrectomized eyes were similar to those in nonvitrectomized eyes. Our data do not support the use of different dosing regimens of ranibizumab in vitrectomized eyes.