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Sergio Mangiafico, Salvatore Cuzzocrea, Danilo Aleo, Barbara Melilli, Maria Grazia Saita, Melina Cro, Sebastiano Mangiafico; Dorzolamide/Latanoprost Association in a New Drug-Delivery System. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2007.
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The study was performed to evaluate the IOP-lowering effect of dorzolamide in combination with latanoprost in a new ocular topical drug-delivery system.
IOP was measured using an applanation tonometer after topical application of 0.4% oxybuprocaine for corneal anesthesia. Normotensive Rabbits Experiment (NRE). 18 male New Zealand White rabbits were divided into 3 groups of 6 animals and treated with 30 μl of 2% Dorzolamide (Trusopt,Merck), 0.005% Latanoprost (Xalatan,Pfizer) and Dorzolamide (2%)/Latanoprost (0.005%) association in the new palmitoylethanolamide/cyclodextrin/hyaluronic acid drug-delivery system (MDV COMBO). Saline was instilled in the controlateral eye (control eye). IOP was measured 30,60,120,180 and 240min after instillation. Hypertensive Rabbits Experiment (HRE). Ocular hypertension was induced into 3 groups of 6 male New Zealand White rabbits by injection of 0.1ml hypertonic saline (5% NaCl) into the vitreous body. The IOP (basal value) was measured, the hypertonic saline was injected and Trusopt, Xalatan and MDV COMBO were applied immediately after the vitreous injection. Saline was instilled in the controlateral eye (control eye). IOP was measured 60 and 120min after instillation.
NRE Trusopt slightly reduced IOP vs saline (∆IOP -1.2±0.6mmHg at 60min, -1.3±0.8mmHg at 120min and -1.8±0.6mmHg at 180min). Small variations were found in the Xalatan group (∆IOP was -1.5±0.7mmHg at 120min, -1.7±0.8mmHg at 180 min and -2.0±0.7mmHg at 240min). MDV-COMBO group showed higher differences (∆IOP -1.7±0.8mmHg at 30min, -2.3±0.7mmHg at 60min, -3.2±0.2mmHg at 120min, -2.5 ± 1.0mmHg at 180min and -1.2±0.7mmHg at 240min). HRE The increase in the IOP was 16±2.0mmHg 60min and 12.4±1.5mmHg 120min after hypertonic saline injection. In the Trusopt group the IOP increase was 12.4±1.5mmHg (-25%) at 60min and 8.7±1.2mmHg (-30%) at 120min. In the Xalatan group 11.4±2.0mmHg (-31%) and 8.5±2.0mmHg (-32%). In the MDV COMBO 8.5±1.5mmHg (-49%) and 6.1±2.1mmHg (-51%).
Trusopt and Xalatan showed a low hypotensive effect in NRE. The higher effect of the MDV-COMBO may be explained with the potentially higher penetration of the actives due to the higher mucoadhesivity of the new drug-delivery system. The results on the HRE confirmed the much higher hypotensive effect of MDV-COMBO.
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