Intravitreal acetylsalicylic acid in silicone oil: pharmacokinetics and evaluation of its safety by ERG and histology.
BACKGROUND
A new method of intravitreal drug delivery of acetylsalicyclic acid (AS) in silicone oil was investigated for safety and for its pharmacokinetics in the posterior pole of the eye.


METHODS
The AS was mixed in silicone oil to a concentration of 1.67 mg/ml. After vitrectomy, 15 NZW rabbits received an intravitreal injection of AS/silicone oil suspension. Clinical examination, pre- and postoperative electroretinography (ERG) and histology were performed. The pharmacokinetics of the distribution of salicylic acid was determined by HPLC analysis at 6 h, 24 h and 5 days in optic nerve, retina, choroid, vitreous, and blood.


RESULTS
Clinical examination and histology revealed no adverse effects or signs of toxicity. The ERGs showed no significant difference between the pre- and postoperative results. The salicylic acid concentrations demonstrated peak values in the residual vitreous (640.0 micrograms/ml), choroid (446.0 ng/mg) and retina (281.3 ng/mg) at 6 h. At 24 h, the salicylic acid concentration decreased to 20.9 micrograms/ml in the residual vitreous and to 38.5 ng/mg in the retina. At 5 days the retinal level was still 48.1 ng/mg.


CONCLUSIONS
AS delivery by intravitreal administration of loaded silicone oil is a safe method and results in high concentrations of salicylic acid in the posterior segment of the eye while maintaining low blood levels.
Kralinger
M T
MT
Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami, 1638 NW 10 Avenue, Miami, FL 33136, USA.
Hamasaki
D
D
Kieselbach
G F
GF
Voigt
M
M
Parel
J M
JM
D000818:Animals; D001241:Aspirin / Q000493:pharmacokinetics*; D001682:Biological Availability; D002829:Choroid / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004596:Electroretinography; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012449:Safety; D012827:Silicone Oils; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology
D016861:Cyclooxygenase Inhibitors; D005343:Fibrinolytic Agents; D012827:Silicone Oils; D001241:Aspirin