title: Ocular aspirin distribution: a comparison of intravenous, topical, and coulomb-controlled iontophoresis administration.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics and safety of aspirin delivered by a single, noninvasive, transscleral, coulomb-controlled iontophoresis (CCI) treatment; topical application; or by one intravenous (IV) injection.
  
  
  METHODS
  Forty-one adult New Zealand White rabbits received either a single IV injection, topical, or CCI administration of aspirin at a concentration of 10 mg/mL. Histologic evaluation was performed in four CCI-treated eyes to assess safety. Pharmacokinetic distribution in all ocular tissues and fluids was studied at 0.5, 1, 2, 4, 6, and 8 hours after the treatments. Immediately after death, the eyes were dissected and salicylic acid (SA) concentration was determined by HPLC analysis. Blood was sampled at 0.5, 1, 2, 4, 6, and 8 hours, and plasma SA levels for systemic distribution were measured by HPLC analysis.
  
  
  RESULTS
  No tissue damage was observed clinically or histologically. SA was found in all tissues and fluids throughout the study period of 8 hours. The highest concentrations of SA were observed with CCI immediately after treatment for all tissues and were the highest SA tissue peaks obtained by the studied delivery methods. IV administration demonstrated a delayed tissue peak of salicylate at 2 hours after administration. At 8 hours, ocular SA concentrations were in the same range for CCI and IV administration. IV injection resulted in blood plasma levels up to 28 times higher than CCI and remained significantly elevated until 8 hours after the treatments.
  
  
  CONCLUSIONS
  CCI is a safe and effective method of administering aspirin to the eye while avoiding the systemic side effects associated with IV injection.
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000295:instrumentation; D004867:Equipment Design; D005123:Eye / Q000378:metabolism*; D007275:Injections, Intravenous; D007478:Iontophoresis / Q000379:methods; D011817:Rabbits; D012449:Safety; D014018:Tissue Distribution
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin