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Efficacy and Pharmacokinetics of Intravitreal Nonsteroidal Anti-Inflammatory Drugs for Intraocular Inflammation
  1. David E Baranano1,
  2. Stephen J Kim2,
  3. Henry F Edelhauser1,
  4. Chandrasekar Durairaj3,
  5. Uday Kompella3 and
  6. James T Handa4
  1. 1 Emory Univeristy, United States;
  2. 2 Vanderbilt University, United States;
  3. 3 University of Colorado, United States;
  4. 4 Johns Hopkins University, United States
  1. * Corresponding author; email: dbaranan{at}jhmi.edu

Abstract

Objective: To determine the efficacy and pharmacokinetics of intraocularly delivered nonsteroidal anti-inflammatory drugs (NSAID) in an animal model of ocular inflammation.

Methods: Lipopolysaccharide was injected into the vitreous of rabbit eyes to induce inflammation. Treated eyes were injected with 3 mg of ketorolac or 0.3 mg of diclofenac. Twenty-four hours later, total leukocyte concentrations and prostaglandin E2 concentrations were determined. For intraocular pharmacokinetics, 0.1 ml of ketorolac (3 mg) and 0.1 ml of diclofenac (0.3 mg) were injected into rabbit eyes. Reverse-phase high performance liquid chromatography was used to analyze drug levels within the retina/choroid at 0.25 (15 minutes), 1, 2, 4, 24, and 48 hours after injection.

Results: Eyes treated with ketorolac and diclofenac demonstrated reduced aqueous leukocyte concentrations of 62% and 64% respectively, compared to untreated controls (P < 0.05.) Ketorolac and diclofenac reduced aqueous prostaglandin E2 levels by 85% (P < 0.005) and 59% (P < 0.005), respectively. Ketorolac and diclofenac achieved a peak vitreous concentration of 234 and 73 µg/ml, respectively. After 48 hours, ketorolac was barely detectable (0.06 µg/ml) in the vitreous and diclofenac was not detected. The peak concentration of each drug in the retina/choroid was 201µg/g for ketorolac and 4.1 µg/g for diclofenac. Both drugs were undetectable in the retina/choroid after 48 hours.

Conclusions: Both ketorolac and diclofenac have potent anti-inflammatory effects after intraocular injection. Pharmacokinetic analysis demonstrated good penetration into the retina/choroid, but rapid clearance by 48 hours.

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