The safety, pharmacokinetics, and efficacy of intraocular celecoxib.
OBJECTIVE
To determine safety, pharmacokinetics, and anti-inflammatory effects of intraocular celecoxib.


METHODS
The right eye of animals was injected with 1.5, 3, or 6 mg celecoxib prepared in dimethyl sulfoxide (DMSO). Left eyes served as controls and received 0.1 mL DMSO. Electroretinograms (ERG) were obtained at baseline and at 1, 4, and 12 weeks, and eyes were enucleated afterward for histopathologic analysis. For pharmacokinetics, 3 mg celecoxib was injected, and vitreous and retina/choroid drug levels were then analyzed at specific time points. For efficacy, 1 μg lipopolysaccharide was injected to induce inflammation; the right eye was then injected with 3 mg celecoxib (six eyes) or 2 mg triamcinolone acetonide (six eyes) and the left eye with saline. Twenty-four hours later, aqueous fluid was removed, and total leukocyte concentration and prostaglandin E2 (PGE2) concentration were determined.


RESULTS
Histologic and ERG studies demonstrated no signs of retinal or optic nerve toxicity. After a single 3-mg injection, vitreous (0.06 μg/mL) and retina/choroid (132.31 μg/g) celecoxib concentrations at 8 weeks exceeded median inhibitory concentration. Treatment with celecoxib and triamcinolone significantly reduced total leukocyte count by 40% (P = 0.02) and 31% (P = 0.01), respectively. Reduction in PGE2 levels paralleled reduction in leukocyte counts (P < 0.05). There was no increase in intraocular pressure, but cataract formation was observed at higher concentrations.


CONCLUSIONS
Intraocular injection of celecoxib appeared to be nontoxic and demonstrated excellent penetration into the retina/choroid and sustained drug levels out to 8 weeks. Celecoxib demonstrated potent anti-inflammatory effects, but there was an association with cataract formation at higher doses.
Department of Ophthalmology, Vanderbilt University, Nashville, Tennessee.
Stephen J
SJ
Kim
Hassanain
H
Toma
Rohan
R
Shah
Uday B
UB
Kompella
Sunil K
SK
Vooturi
Jinsong
J
Sheng
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004596:Electroretinography; D058449:Intravitreal Injections; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
NSAIDs; celecoxib; inflammation; intravitreal drug delivery; prostaglandins