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  • Title: Efficacy and pharmacokinetics of intravitreal non-steroidal anti-inflammatory drugs for intraocular inflammation.
    Author: Barañano DE, Kim SJ, Edelhauser HF, Durairaj C, Kompella UB, Handa JT.
    Journal: Br J Ophthalmol; 2009 Oct; 93(10):1387-90. PubMed ID: 19628498.
    Abstract:
    OBJECTIVE: To determine the efficacy and pharmacokinetics of intraocularly delivered non-steroidal anti-inflammatory drugs 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 leucocyte 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 analyse drug levels within the retina/choroid at 0.25 (15 min), 1, 2, 4, 24, and 48 h after injection. RESULTS: Eyes treated with ketorolac and diclofenac demonstrated reduced aqueous leucocyte concentrations of 62% and 64% respectively, compared with 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 microg/ml, respectively. After 48 h, ketorolac was barely detectable (0.06 microg/ml) in the vitreous, and diclofenac was undetectable. The peak concentration of each drug in the retina/choroid was 201 microg/g for ketorolac and 4.1 microg/g for diclofenac. Both drugs were undetectable in the retina/choroid after 48 h. 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 h.
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