CONTROLLED OCULAR TIMOLOL DELIVERY - SYSTEMIC ABSORPTION AND INTRAOCULAR-PRESSURE EFFECTS IN HUMANS

Timolol eyedrops may cause systemic side-effects in glaucoma patients due to absorption of the drug into systemic circulation. In a previous study, timolol concentrations in plasma were reduced if timolol was a dministered in ocular inserts instead of eyedrops. We compared the int raocular pressure lowering effect and systemic absorption of timolol i nserts to those of 0.5 % timolol eyedrops in humans. Inserts of silico ne tubing released 90.3+/-13.9 mu g of timolol in 24 hours in vivo. Ti molol inserts afforded similar decreases in intraocular pressure in op en-angle glaucoma patients as did b.i.d. eyedrops, but produced lower peak timolol concentrations in plasma, 0.70+/-0.10 ng/ml and 0.24+/-0. 05 ng/ml, respectively. After eyedrops, peak concentrations were achie ved at 15.0+/-2.2 min, while application of an insert resulted in a de layed peak (t(max) = 623+/-195 min). The insert resulted in a higher s ystemically absorbed fraction of the timolol dose than the eyedrop, bu t the peak timolol concentration and daily absorbed amount of timolol were decreased. The release rate of timolol from the inserts in vivo w as only slightly less than that in vitro. Silicone devices are useful for clinical testing of controlled delivery properties of ocular drugs .