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Updated: Jul 15, 2026
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Ocular pharmacokinetics of subconjunctivally administered cyclosporine in the rabbit
G S Kalsi1, G Gudauskas, N Bussanich
1Department of Ophthalmology, University of British Columbia, Vancouver.
Abstract:
The authors assessed the ocular toxicity and pharmacokinetics of subconjunctivally and intravenously administered cyclosporine in New Zealand white rabbits. Fifteen rabbits received a subconjunctival injection of 5 (five animals), 10 (five animals) or 25 (five animals) mg of cyclosporine in 0.1 mL (intravenous solution of Sandimmune [50 mg/mL]); 5 mg was found to be the maximum tolerable dose. This dose was given as a bolus to 36 other rabbits either subconjunctivally (18 animals) or intravenously (18 animals). In both groups the cyclosporine concentrations in the ocular compartments, blood and urine were measured by means of high-pressure liquid chromatography at 0.5, 1, 2, 4, 8 and 12 hours, three animals being assessed at each interval. Subconjunctival administration resulted in peak cyclosporine concentrations of 718 ng/mL in the aqueous humour and 1078 ng/mL in the vitreous humour, compared with no detectable levels in the aqueous humour and a peak concentration of 292 ng/mL in the vitreous following intravenous administration. The peak blood cyclosporine levels were 10 times lower after subconjunctival injection than after intravenous injection. The results indicate that subconjunctival administration is superior to intravenous administration in enhancing the ocular absorption of cyclosporine while minimizing systemic exposure in the rabbit.
Insights
Subconjunctival cyclosporine delivery enhances ocular absorption and minimizes systemic exposure in rabbits compared to intravenous administration. This method offers a promising route for targeted ocular drug delivery.
Area of Science:
- Ophthalmology
- Pharmacology
- Drug Delivery
Background:
- Cyclosporine is an immunosuppressant used in treating various ocular conditions.
- Understanding its ocular pharmacokinetics is crucial for optimizing treatment efficacy and safety.
Purpose of the Study:
- To evaluate the ocular toxicity and pharmacokinetics of subconjunctival versus intravenous cyclosporine administration in rabbits.
- To compare ocular and systemic drug concentrations following different administration routes.
Main Methods:
- New Zealand white rabbits received subconjunctival or intravenous injections of cyclosporine.
- Cyclosporine concentrations in aqueous humor, vitreous humor, blood, and urine were measured using high-pressure liquid chromatography at various time points.
- Maximum tolerable dose and peak concentrations were determined.
Main Results:
- Subconjunctival administration yielded significantly higher peak cyclosporine concentrations in aqueous (718 ng/mL) and vitreous (1078 ng/mL) humor compared to intravenous administration.
- Intravenous administration resulted in no detectable aqueous humor levels and a peak vitreous concentration of 292 ng/mL.
- Peak blood cyclosporine levels were 10 times lower after subconjunctival injection than after intravenous injection.
Conclusions:
- Subconjunctival cyclosporine administration demonstrates superior ocular absorption compared to intravenous delivery.
- This route effectively enhances drug concentration within ocular tissues while reducing systemic exposure in rabbits.
- Subconjunctival administration represents a more efficient method for achieving therapeutic cyclosporine levels in the eye.
