Intravitreal acetylsalicylic acid in silicone oil: pharmacokinetics and evaluation of its safety by ERG and histology

Graefes Arch Clin Exp Ophthalmol. 2001 Mar;239(3):208-16. doi: 10.1007/s004170100255.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspirin / pharmacokinetics*
  • Biological Availability
  • Choroid / metabolism
  • Choroid / pathology
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase Inhibitors / pharmacokinetics*
  • Drug Delivery Systems*
  • Electroretinography
  • Female
  • Fibrinolytic Agents / pharmacokinetics*
  • Male
  • Rabbits
  • Retina / metabolism
  • Retina / pathology
  • Safety
  • Silicone Oils*
  • Vitrectomy
  • Vitreous Body / metabolism*
  • Vitreous Body / pathology

Substances

  • Cyclooxygenase Inhibitors
  • Fibrinolytic Agents
  • Silicone Oils
  • Aspirin