Calcium channel blockers have complex actions on aqueous humour dynamics that seem to depend on the route of drug administration. When applied topically, verapamil and nifedipine effectively lower intraocular pressure. However, these drugs also produce a slight reduction in aqueous humor outflow through the trabecular meshwork whereby they could modify the effect of other drugs on intraocular pressure. As calcium channel blockers could be effective in the management of ocular hypertension and low-tension glaucoma, the aim of the present work was to assess the interaction between verapamil and timolol when both drugs are topically applied to the eye of albino rabbits.
Intraocular pressure was measured with a manual applanation tonometer. The effects of 5-6 different doses of each drug alone and the effects of five mixtures of both drugs at fixed concentration ratios (timolol: verapamil 4: 1, 2: 1, 1 : 1, 1 : 2 and 1:4) were evaluated. After measuring baseline intraocular pressure, one 50 gl drop of the different solutions was instilled in the left eye. Measures of the intraocular pressure were repeated at intervals of 30 min until the maximal effect was reached. Each set of experiments was carried out in a group of 9-11 rabbits. Dose-response curves were fitted with a nonlinear regression microcomputer programme. The median effect plot was constructed as proposed by Chou and Talalay (1981, 1983, 1984). In order to analyse the nature of the interaction between both drugs, the observed effect was compared with the theoretically expected one and the combination indices, that relate the doses of verapamil and timolol present in the mixtures with the doses of both drugs separately J. Santaf+ (sz~)" M.