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AIM: Presented experimental work was aimed to examine a pharmacokinetic efficiency of 0.5% Timolol mixtures with 4 free amino acids, present in conjunctival sac: lysine, arginine, glycine or taurine on the IOP physiological values in rabbits. METHODS: The experimental work was performed on 5 female rabbits of the New Zealand White species. After instillation at 8.00 a.m. into the left conjunctival sac: a) the 10% L-lysine x 2HCl x 2H2O in 0.5% Timolol; b) the 10% L-arginine x HCl in 0.5% Timolol; c) the 10% L-glycine x HCl in 0.5% Timolol; d) the 10% L-taurine x HCl in 0.5% Timolol, the IOP was measured before and in 5th, 15th, 30th, 60th, 120th, 180th and 240th min and in 24 hours. The right eye of the same rabbit was used as control with the instillation of both 0.5% Timolol and amino acids alone into the conjunctival sac. RESULTS: a) The IOP has decreased after mixture of 10% lysine in 0.5% Timolol with two spikes--not significant decrease up to 60th min and a high significant decrease between 120th to 240th min; b) The mixture of 10% arginine in 0.5% Timolol decreased the IOP values with a high significance (from 2.1 to 4 torr); c) The 10% glycine in 0.5% Timolol showed a significant IOP decrease (excluding measurement in 5th min) in all measured times, the biggest IOP decrease was observed in 60th min (mean value 8.5 torr), the decrease was 3.3 torr also in 24th hours; d) The 10% taurine in 0.5% Timolol showed also a significant IOP decrease (excluding measurement in 5th min) in all measured times with maximum in 180th min (with a decrease to 6.7 torr) and the decrease showed a significantly low level--3.3 torr--also in 24 hours. CONCLUSIONS: The results proved that the mixture of antiglaucomatic 0.5% Timolol and amino acid (lysine, arginine, glycine or taurine) contains a new biologically active substance, the "specific bioantiglaucomatic" created by interaction. Compared to the substances alone, mixture of amino acid in the antiglaucomatic decreased the physiologic IOP in rabbits with a high significance. The effect on IOP based on the interaction of the mixture of amino acid with antiglaucomatic is specific and its efficacy together with time was changed depending on the type of amino acid. Our in vitro produced bioantiglaucomatic fulfilled the physiological criteria for the IOP reduction (Fig. 4, Ref 12).
Dr. Z. Olah, Department of Ophthalmology, Faculty of Medicine, Comenius University, Mickiewiczova 13, SK-813 69 Bratislava, Slovakia. olahz@slovanet.sk
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)