Short-term ocular toxicity and eye irritation tests following application of sufentanil in rabbits.

Purpose: To test the safe clinical application of sufentanil as topical ophthalmic drops by examining treated rabbit eyes for ophthalmic irritation signs or short-time toxic reactions.

Methods: Twenty-four rabbits were randomly divided into 8 groups (n = 3): The ocular toxicity at 14 d after eye drop ad- ministration was evaluated in groups 1 to 4, and at 30 d post- administration in groups 5 to 8. Groups 1 and 5 were treated with blank vehicle and served as normal controls. The left eyes of rabbits in groups 2 and 6 were exposed to low-dose sufentanil.(5 μg, 2 drops within 5 min), groups 3 and 7 received moderate-dose sufentanil (7.5 μg, 3 drops within 10 min), and groups 4 and 8 received high-dose sufentanil.(10 μg, 4 drops within 15 min). As self-controls, the right eyes of each rabbit were administered an equivalent amount of sodium chloride (9 g/L) at the same drop intervals. At 14 and 30 d after exposure to sufentanil, ophthalmic irritation signs were evaluated and corneas were stained with fluorescein and observed by slit-lamp microscopy. Corneal endothelial counts were performed and toxic reactions were evaluated.

Results: Multiple parameters were compared in the control and experimental groups by visual inspection and slit-lamp examination at 14 and 30 d after sufentanil administration. No evidence of irritation signs (including corneal opacity, conjunctival congestion, or edema), eye secretions, iris abnormalities, or temporal eye closure were noted. Corneal en- dothelial cell counts did not significantly differ between the control and experimental groups. Light microscopy revealed no pathological or morphological injury to the cornea, conjunctiva, iris, ciliary body, retina, or optic nerve in either group. The same observation outcomes were noted at 14 and 30 d after administration.

Conclusion: Single ocular administration of sufentanil at a dose of 5-10 μg in rabbits yields no ocular irritation or toxic responses at 14 or 30 d following eye drop delivery.