Plasma Pharmacokinetics of Topical 0.1% Diclofenac Sodium and 0.5% Ketorolac Tromethamine in Dogs.

Abstract

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&#x2009;mL, equivalent to one drop of diclofenac or ketorolac into both eyes 4 times daily for 5&#x2009;days (4&#x2009;am, 8&#x2009;am, 12&#x2009;pm, and 4&#x2009;pm). Plasma samples were collected at 5, 15, 30, 60, 120, 240, and 360&#x2009;min after the 4&#x2009;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&#x2009;<&#x2009;0.05). RESULTS: After ophthalmic administration of 0.1% diclofenac, mean t, T, and Coccurred at 3.08&#x2009;&#xb1;&#x2009;0.9&#x2009;h, 121.4&#x2009;&#xb1;&#x2009;2.8&#x2009;h, 0.12&#x2009;&#xb1;&#x2009;0.05 &#x3bc;g/mL, respectively. The mean t, T, and Cafter 0.5% ketorolac administration were 18.5&#x2009;&#xb1;&#x2009;14.6&#x2009;h, 121.6&#x2009;&#xb1;&#x2009;2.0&#x2009;h, 1.8&#x2009;&#xb1;&#x2009;1.7 &#x3bc;g/mL, respectively. The AUCfor diclofenac and ketorolac was 8.97&#x2009;&#xb1;&#x2009;3.73 &#x3bc;g/mL*h and 98.2&#x2009;&#xb1;&#x2009;43.3 &#x3bc;g/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.