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  • Title: Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits.
    Author: Wang M, Liu W, Lu Q, Zeng H, Liu S, Yue Y, Cheng H, Liu Y, Xue M.
    Journal: Retina; 2012; 32(10):2158-64. PubMed ID: 23099451.
    Abstract:
    PURPOSE: To investigate the concentrations and pharmacokinetics of ketorolac in the rabbits by three different routes of administrations: a single intracameral, intravitreal, and suprachoroidal injection. METHODS: Fifty-four New Zealand white rabbits received ketorolac (250 μg/0.05 mL) in one eye by a single intracameral injection (group A, n = 18), single intravitreal injection (group B, n = 18), and single suprachoroidal injection (group C, n = 18). Drug concentrations in the vitreous, retina-choroid (RC), and plasma were determined by the methods of high-performance liquid chromatography at 0.5, 1, 2, 4, 8, and 24 hours after injection. The concentrations in the opposite eyes were also investigated. RESULTS: The mean maximum concentrations (Cmax) of ketorolac in the vitreous and RC were 0.378 ± 0.19 μg/mL and 3.15 ± 0.49 μg/g (at 0.5 hours), respectively, in group A; 156.2 ± 20.74 μg/mL (at 0.5 hours) and 208.0 ± 21.67 μg/g (at 1 hours), respectively, in group B; and 0.873 ± 0.34 μg/mL and 56.71 ± 22.64 μg/g (at 0.5 hours), respectively, in group C. In the RC, the area under the curve (AUC0-t) in group B (866.1 ± 52.67 μg/g·h) was higher (P < 0.01) than that in group C (77.10 ± 25.90 μg/g·h). The elimination half-life (t1/2) in group B (3.09 hours) was longer (P < 0.01) than that in group C (1.19 hours). In the control eyes, a drug level below 2 μg/g was detected in the RC in group C. Plasma concentrations were below 0.4 μg/mL in all 3 groups. Ketorolac was detectable in the RC till 24 hours after the intravitreal injection and 8 hours after the suprachoroidal injection. CONCLUSION: Intravitreal injection of ketorolac produced higher intraocular drug concentrations for a longer period compared with the other two routes. Suprachoroidal injection of ketorolac could reach an effective drug level in the RC with short half-lives and low drug levels in the vitreous. The plasma drug concentrations were low by all three routes.
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