Controlled drug delivery devices for experimental ocular studies with timolol 2. Ocular and systemic absorption in rabbits

Controlled drug delivery was tested as a means to decrease the potentially dangerous systemic drug concentrations which are associated with timolol eyedrop therapy. l-Tumolol (125 μg) was administered in 0.5% eyedrops (25 μl, pH 6.86) and in controlled release silicone tubing devices (dose 57.6 μ;g; release rate 7.2 μg h for 8 h) in the eyes of pigmented rabbits. [³H]Timolol tracer was used in ocular absorption studies and unlabeled timolol dosage forms in systemic absorption studies. [³H]Timolol concentrations were determined in ocular tissues and tear fluid. Beta blocking activity in plasma was determined using a radioreceptor assay. Comparable timolol concentrations were achieved in the iris-ciliary body with silicone tubing devices (57.6 μg) and with eyedrops (125 μg). The relative ocular timolol bioavailability after controlled drug delivery was about 2-fold greater than from eyedrops. In plasma, peak beta-blocking activity was much higher after eyedrop administration (17.16 ± 2.40 ng/ml) than during controlled timolol delivery (< 1.0 ng ml). The results indicate that controlled drug delivery is a viable alternative in improving the therapeutic index of glaucoma therapy with timolol.