ArticlePharmacology research & perspectives2019
Species differences in ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib eye-drops among rats, rabbits and monkeys.
Article in Pharmacology research & perspectives, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Topical Treatment for Retinal Degenerative Pathologies: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Preclinical Ocular Pharmacokinetics and Efficacy of Novel Tivozanib Eye Drops for Neovascular Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2026Article
- Ocular pharmacokinetics of tivozanib eye drops in patients with neovascular age-related macular degeneration: comparison with phase 1 trials of oral tivozanib in solid tumors.International journal of retina and vitreous · 2026Article
- Intravitreal Sustained Release of Dexamethasone from a Self-Healing Injectable Hydrogel: An In Vivo Safety and Release Study.Molecular pharmaceutics · 2025Article
- Nanomedicine-Based Ophthalmic Drug Delivery Systems for the Treatment of Ocular Diseases.International journal of nanomedicine · 2025Review
- QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.Pharmaceutics · 2024Article
- Article
- Ocular and Plasma Pharmacokinetics of Enavogliflozin Ophthalmic Solution in Preclinical Species.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Pharmacokinetics and metabolism of ketoconazole after single ocular instillation in Sprague-Dawley rats.ADMET & DMPK · 2024Article
- Topical Drug Delivery to the Posterior Segment of the Eye.Pharmaceutics · 2022Review
- A Novel Eye Drop Formulation for Potential Treatment of Neovascular Age-Related Macular Degeneration.Translational vision science & technology · 2021Article
- Topical Ketotifen Fumarate Inhibits Choroidal Mast Cell Degranulation and Loss of Retinal Pigment Epithelial Cells in Rat Model for Geographic Atrophy.Translational vision science & technology · 2021Article
- Patient preferences in retinal drug delivery.Scientific reports · 2021Observational
- The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye.Ophthalmology and therapy · 2021Review
- The Role of Eph Receptors and Ephrins in Corneal Physiology and Diseases.International journal of molecular sciences · 2021Review
- Article
- Gelling hypotonic polymer solution for extended topical drug delivery to the eye.Nature biomedical engineering · 2020Article
- Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C.International journal of molecular sciences · 2019Article
- Species differences in ocular pharmacokinetics and pharmacological activities of regorafenib and pazopanib eye-drops among rats, rabbits and monkeys.Pharmacology research & perspectives · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age-related macular degeneration (AMD) is the leading cause of severe vision impairment in patients over the age of 60 years. Choroidal neovascularization (CNV) is the hallmark of neovascular AMD and vascular endothelial growth factor (VEGF) plays a causal role in the formation of CNV. Although regorafenib and pazopanib, small molecule VEGF receptor (VEGFR) inhibitors, were developed as eye-drops, their efficacies were insufficient in clinical. 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 posterior 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 regorafenib 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 reason 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.