Pharmacokinetics and efficacy of intraocular flurbiprofen.

Abstract

PURPOSE:

Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes.

METHODS:

For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings.

RESULTS:

No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes.

CONCLUSIONS:

Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.

• Authors: S Blazaki, C Tsika, M Tzatzarakis, E Naoumidi, A Tsatsakis, C Tsatsanis, Miltiadis K Tsilimbaris
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 255 Issue 12 Pg. 2375-2380 (Dec 2017) ISSN: 1435-702X [Electronic] Germany
• PMID: 28963579 (Publication Type: Journal Article)

Chemical References

• Cyclooxygenase Inhibitors
• Flurbiprofen

Topics

• Animals
• Cyclooxygenase Inhibitors (administration & dosage, pharmacokinetics)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Endophthalmitis (complications, drug therapy, metabolism)
• Flurbiprofen (administration & dosage, pharmacokinetics)
• Intravitreal Injections
• Macular Edema (diagnosis, drug therapy, etiology)
• Ophthalmoscopy
• Posterior Eye Segment
• Rabbits
• Treatment Outcome
• Vitreous Body (metabolism, pathology)