Species differences in ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib eye ‐drops among rats, rabbits and monkeys

In this study, we evaluated ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib after ocular instillation in multiple animal species. In rats, both regorafenib and pazopanib showed high enough concentrations in the posterior eye tissues to inhibit VEGFR. In laser‐induced rat CNV model, regorafenib showed clear reduction in CNV area. On the other hand, the concentrations of regorafenib and pazopanib in the poster ior eye tissues were much lower after ocular instillation in rabbits and monkeys compared to those in rats. Pazopanib did not show any improvement in monkey model. Regorafenib was nano‐crystalized to improve its drug delivery to the posterior eye tissues. The nano‐crystalized formulation of rego rafenib showed higher concentrations in the posterior segments in rabbits compared to its microcrystal suspension. From these studies, large interspecies differences were found in ocular delivery to the posterior segments after ocular instillation. Such large interspecies difference could be the rea son for the insufficient efficacies of regorafenib and pazopanib in clinical studies. Nano‐crystallization was suggested to be one of the effective ways to overcome this issue.
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research