Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits.

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.