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Afshin Shafiee, Lyle Bowman, Eddie Hou, Kamran Hosseini; Ocular Pharmacokinetics of 0.2% and 0.4% Ketorolac Tromethamine Formulated in DuraSite or DuraSite 2 Delivery Systems Compared to Acular LS in Rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):116.
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To compare the ocular penetration of 0.2% and 0.4% ketorolac formulated in DuraSite or the new generation, DuraSite 2, delivery systems to Acular LS (0.4% ketorolac).
The left eye of male and female rabbits (n=32/group) received either a single topical instillation of ketorolac 0.2% or ketorolac 0.4% formulated in DuraSite, or DuraSite 2, or Acular LS. At predetermined timepoints (0.25, 0.5, 1, 2, 4, 6, 12, and 24 hours), 4 rabbits/group/timepoint were sacrificed and the ketorolac levels in the aqueous humor (AH) were quantified using LC-MS/MS methodology. PK parameters (Cmax, Tmax, AUC0.25-24h) were determined.
Ketorolac 0.4% formulated in DuraSite 2 achieved the highest Cmax (1889 ± 884 ng/mL) and AUC (6836 ng/mL*h) values, an increase of 6.9- and 4.8-fold over Acular LS which had the lowest Cmax (275 ± 83 ng/mL) and AUC (1424 ng/mL*h) values, respectively. Ketorolac 0.2% formulated in DuraSite 2 had Cmax (1077 ± 415 ng/mL) and AUC (4490 ng/mL*h) values that were 3.9- and 3.2-fold higher than Acular LS, respectively. Ketorolac 0.2% and 0.4% formulated in DuraSite also provided better AH pharmacokinetics with Cmax values that were 2.9- and 4.4-fold higher than Acular LS, respectively, and AUC values that were 2.3- and 4.0-fold higher than Acular LS, respectively.
Ketorolac formulated in DuraSite markedly improved drug delivery kinetics to the AH compared with Acular LS; the new generation delivery system, DuraSite 2, showed enhanced penetration over DuraSite. DuraSite 2 formulation may allow a major reduction in the dosing regimen or lowering of the ketorolac levels in the ophthalmic formulation; it may potentially lessen the side effect profiles associated with the topical use of ketorolac.
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