Gastrointestinal Adverse Effects of Ophthalmic Nonsteroidal Anti-inflammatory Drugs in Dogs

Abstract: Background—While gastrointestinal (GI) ulceration is a well-recognized adverse effect associated with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), the risk of systemic adverse effects from topical ophthalmic application of NSAIDs is unknown.

Hypothesis/objectives—To investigate systemic concentrations and GI adverse effects of ophthalmic ketorolac 0.5% and diclofenac 0.1%.

Animals—11 healthy purpose-bred adult beagle dogs.

Methods—Dogs were randomly assigned to receive either ketorolac (N=6) or diclofenac (N=5) one drop in both eyes four times daily for 28 days in a parallel design. Upper GI endoscopy was performed on Day 0 and Day 28 with mucosal lesion scores (0-7) assigned to each region evaluated. Blood samples were collected 15 minutes following eyedrop administration on Day 14, 21, and 28 for drug quantification in plasma using high-performance liquid chromatography/mass spectrometry.

Results—Erosions and/or ulcers developed in 4/6 ketorolac-treated dogs and 1/5 diclofenac-treated dogs. Post-treatment mucosal lesion score for the antrum was higher in the ketorolac group than in the diclofenac group (P=0.009) but not significantly different for any other region. Vomiting and decreased appetite events were observed uncommonly and were not significantly different between treatment groups. Ketorolac and diclofenac were detected in the plasma at all timepoints (ketorolac median 173.5-191 ng/ml, diclofenac median 20.6-27.5 ng/ml).

Conclusions and clinical importance—Ketorolac and diclofenac were absorbed systemically after ophthalmic administration and associated with the development of GI ulceration and erosion, with higher plasma concentrations and more severe GI lesions associated with ketorolac.