Fibrinolytic Capacity of Desmoteplase Compared to Tissue Plasminogen Activator in Rabbit Eyes

Autor: Simon A. Pot, Katrin Voelter, Christoph Tappeiner, Fernando Laguna Sanz, Deborah Bruetsch, Karina Klein, Nicole Borel
Přispěvatelé: University of Zurich, Voelter, Katrin
Rok vydání: 2019
Předmět:
0301 basic medicine
Administration
Topical

10184 Institute of Veterinary Pathology
Pharmacology
Eye
Tissue plasminogen activator
Fibrin
Plasminogen Activators
03 medical and health sciences
0302 clinical medicine
Fibrinolytic Agents
In vivo
medicine
2736 Pharmacology (medical)
Animals
Desmoteplase
Pharmacology (medical)
610 Medicine & health
630 Agriculture
Dose-Response Relationship
Drug

biology
business.industry
Rabbit (nuclear engineering)
2731 Ophthalmology
medicine.disease
10226 Department of Molecular Mechanisms of Disease
Ophthalmology
3004 Pharmacology
030104 developmental biology
Tissue Plasminogen Activator
Toxicity
030221 ophthalmology & optometry
biology.protein
570 Life sciences
Female
10090 Equine Department
Rabbits
Injections
Intraocular

Ophthalmic Solutions
business
Uveitis
medicine.drug
Zdroj: Journal of Ocular Pharmacology and Therapeutics. 35:66-75
ISSN: 1557-7732
1080-7683
DOI: 10.1089/jop.2018.0070
Popis: PURPOSE Desmoteplase (DSPA) was evaluated and compared with tissue plasminogen activator (t-PA) for its intraocular fibrinolytic effect and short-term toxicity in an in vivo study using rabbit eyes. METHODS Fibrin clots were induced in the anterior chamber of 44 rabbit eyes, and drug efficacy was measured by clot size reduction over 24 h. Topical DSPA eye drops (1.4 and 2 mg/mL) were compared with vehicle solution in a multiple-drop regimen in 8 animals per group. Intracameral injections of 0.6 μg DSPA (n = 14) and 25 μg t-PA (n = 14) were evaluated for their fibrinolytic efficacy. Animals were euthanized 24 h after drug application. RESULTS No significant differences were seen between topically treated DSPA and vehicle-treated animals. Intracameral t-PA had a higher fibrinolytic efficacy than DSPA at early time points, but no significant difference was seen between both groups at 24-h postapplication. Animals with t-PA treatment demonstrated significantly more side effects compared with DSPA-treated animals. DSPA showed no-to-mild side effects after topical and intracameral treatment. Histologically, no toxic effects were observed in any globe. CONCLUSIONS DSPA is a promising drug with fewer side effects and similar fibrinolytic efficacy compared with t-PA 24 h after intracameral application in rabbit eyes at the tested concentration. Drug efficacy might be improved by increasing intracameral DSPA doses.
Databáze: OpenAIRE