Comparison of Topical and Intravenous Administration of WIN 55-212-2 in Normotensive Rabbits

Abstract

Objective: This study compares the effect of topical versus intravenous (IV) administration of synthetic WIN 55-212–2 (WIN) or timolol on intraocular pressure (IOP). Methods: WIN or timolol were administered either topically or by IV in normotensive New Zealand white rabbits. IOP was measured at baseline and 30, 60, and 120 min after administration (n = 4 per group). Blood pressure (BP) and heart rate (HR) were measured concomitantly with IOP. Results: IV administration of 0.1 mg/kg WIN reduced IOP by 30% after 30 min, which continued to decline for up to 120 min. Timolol injection (25 μ g/kg) also reduced IOP by 25% after 30 min but was not sustained. In comparison, both topical WIN (1.0%) and timolol (0.5%) reduced IOP by 20% from baseline after 30 min. IV injection of either WIN or timolol significantly reduced HR to 155.4 ± 11.4 bpm and 165.9 ± 11.1 bpm, respectively, from a baseline of 256.3 ± 9.9 bpm. Topical administration was well tolerated and did not affect behavior, BP, or HR. Conclusion: Topical administration of either WIN or timolol did not decrease IOP as much as IV administration, but the lack of systemic or local toxicity could make it the safer alternative.