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 acetylsalicylic a cid (AS) in silicone oil was investigated for safety and for its pharmacoki netics in the posterior pole of the eye. h Methods: The AS was mixed in sil icone oil to a concentration of 1.67 mg/ml. After vitrectomy, 15 NZW rabbit s received an intravitreal injection of AS/silicone oil suspension. Clinica l examination, pre- and postoperative electroretinography (ERG) and histolo gy were performed. The pharmacokinetics of the distribution of salicylic ac id 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 his tology revealed no adverse effects or signs of toxicity. The ERGs showed no significant difference between the pre- and postoperative results, The sal icylic acid concentrations demonstrated peak values in the residual vitreou s (640.0 mug/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 mug/ml in the res idual vitreous and to 38.5 ng/mg in the ret-ina. At 5 days the retinal leve l was still 48.1 ng/mg. Conclusions: AS delivery by intravitreal administra tion of loaded silicone oil is a safe method and results in high concentrat ions of salicylic acid in the posterior segment of the eye while maintainin g low blood levels.