Veterinary ophthalmology · 2025
Plasma Pharmacokinetics of Topical 0.1% Diclofenac Sodium and 0.5% Ketorolac Tromethamine in Dogs.
СтатьяRandomized Controlled Trial, VeterinaryНазвание и аннотация: Перевод в очереди
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Peraza Jacqueline, Ross Matthew K, Langston Vernon C, Wills Robert, Fischer Danielle, Cassen Christine, Betbeze Caroline
Аннотация
OBJECTIVE: To determine plasma concentrations of ophthalmic 0.1% (w/v) diclofenac sodium and 0.5% (w/v) ketorolac tromethamine following 4 times daily ophthalmic administration in healthy dogs.
ANIMALS STUDIED: Eight healthy research Beagles.
PROCEDURES: A prospective, masked, randomized, crossover study was conducted. Eight dogs were randomly assigned to a diclofenac or ketorolac group (4 dogs per group). Plasma was collected before drug administration (time 0/baseline). Each dog received 0.05 mL, equivalent to one drop of diclofenac or ketorolac into both eyes 4 times daily for 5 days (4 am, 8 am, 12 pm, and 4 pm). Plasma samples were collected at 5, 15, 30, 60, 120, 240, and 360 min after the 4 pm treatment on Days 1 and 5. Plasma concentrations (ng/mL) were quantified by liquid chromatography-mass spectrometry and analyzed with noncompartmental pharmacokinetic analysis. A Wilcoxon signed rank test was used to determine statistical significance (p < 0.05).
RESULTS: After ophthalmic administration of 0.1% diclofenac, mean t1/2, Tmax, and Cmax occurred at 3.08 ± 0.9 h, 121.4 ± 2.8 h, 0.12 ± 0.05 μg/mL, respectively. The mean t1/2, Tmax, and Cmax after 0.5% ketorolac administration were 18.5 ± 14.6 h, 121.6 ± 2.0 h, 1.8 ± 1.7 μg/mL, respectively. The AUC0-∞ for diclofenac and ketorolac was 8.97 ± 3.73 μg/mL*h and 98.2 ± 43.3 μg/mL*h, respectively.
CONCLUSIONS: Diclofenac and ketorolac were rapidly absorbed systemically after ophthalmic administration. The half-life of topical ketorolac is six times longer than that of diclofenac.
ANIMALS STUDIED: Eight healthy research Beagles.
PROCEDURES: A prospective, masked, randomized, crossover study was conducted. Eight dogs were randomly assigned to a diclofenac or ketorolac group (4 dogs per group). Plasma was collected before drug administration (time 0/baseline). Each dog received 0.05 mL, equivalent to one drop of diclofenac or ketorolac into both eyes 4 times daily for 5 days (4 am, 8 am, 12 pm, and 4 pm). Plasma samples were collected at 5, 15, 30, 60, 120, 240, and 360 min after the 4 pm treatment on Days 1 and 5. Plasma concentrations (ng/mL) were quantified by liquid chromatography-mass spectrometry and analyzed with noncompartmental pharmacokinetic analysis. A Wilcoxon signed rank test was used to determine statistical significance (p < 0.05).
RESULTS: After ophthalmic administration of 0.1% diclofenac, mean t1/2, Tmax, and Cmax occurred at 3.08 ± 0.9 h, 121.4 ± 2.8 h, 0.12 ± 0.05 μg/mL, respectively. The mean t1/2, Tmax, and Cmax after 0.5% ketorolac administration were 18.5 ± 14.6 h, 121.6 ± 2.0 h, 1.8 ± 1.7 μg/mL, respectively. The AUC0-∞ for diclofenac and ketorolac was 8.97 ± 3.73 μg/mL*h and 98.2 ± 43.3 μg/mL*h, respectively.
CONCLUSIONS: Diclofenac and ketorolac were rapidly absorbed systemically after ophthalmic administration. The half-life of topical ketorolac is six times longer than that of diclofenac.