Abstract
Anti-angiogenic antibodies are widely used in the treatment of neovascular macular degeneration. Human antibody targeting C-type lectin domain family 14 member A (CLEC14a) is potential therapeutic agents owing to its antiangiogenic activity. In the present study, we aimed to predict the human intraocular pharmacokinetic (PK) properties of an anti-CLEC14a antibody. I-125 labeled aflibercept and anti-CLEC14a antibody were intravitreally injected into mice, rats, and rabbits. Single photon emission computed tomography/computed tomography imaging was performed, and the intraocular radioactivity concentration (%ID/ml) was obtained. The PK parameters in those three animal species were obtained by compartmental analysis. The PK parameters in humans were estimated by allometric scaling of the animal PK parameters with consideration of the hydrodynamic radius of the antibody. The mean half-life values of intraocular I-125-labeled aflibercept in mice, rats, and rabbits were 1.13 days, 1.25 days, and 4.91 days, respectively, by analysis with a one-compartment model. The predicted human half-life of intraocular aflibercept was 5.75 days based on vitreal volume by allometric scaling. The half-life values of intraocular I-125-labeled anti-CLEC14a in mice, rats and rabbits were 1.05 days, 1.84 days, and 6.37 days, respectively, by analysis with a one-compartment model. The predicted human half-life of intraocular anti-CLEC14a was 10.29 days based on vitreal volume. According to the hydrodynamic volume of the anti-CLEC14a, the predicted human half-life of intraocular anti-CLEC14a was 9.81 days. The PK characteristics of the intraocular anti-CLEC14a antibody were evaluated noninvasively in animals using I-125 labeling, and the intraocular PK characteristics in humans were predicted using these animal data. This methodology can be applied for the development of new antiangiogenic antibodies to treat macular degeneration.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
