Dose response for travoprost® in the glaucomatous beagle.

OBJECTIVE: To evaluate the changes in intraocular pressure (IOP) and pupil size in 12 Beagles with inherited glaucoma after instillations of 0.033, 0.0033, 0.001, 0.00033, and 0.0001% travoprost (Travatan®-Alcon Laboratories, Inc., Ft Worth, TX, USA) in multiple single-dose studies. PROCEDURES: Intraocular pressure and pupil diameter (PD) measurements were obtained at 9 am, 12 pm, 3 pm, and 9 am the following day (24 h) in two groups of six glaucoma dogs. After 7 days, the vehicle or concentration was repeated in the contralateral eye of the same animals. RESULTS: Concentrations of 0.00033, 0.001, and 0.0033% travoprost significantly lowered IOP and PD, but the 0.0001% concentration provided limited IOP changes, although PD changes were still significant. This suggests travoprost is effective in the dog to lower IOP and reduce pupil size at concentrations starting between 0.0001 and 0.00033%. CONCLUSIONS: The dose response for travoprost in the glaucomatous Beagle indicates this model is highly sensitive to this group of drugs, even at concentrations as low as 0.00033% (1/12 the commercially available concentration).

Drug delivery by contact lens in spontaneously glaucomatous dogs.

PURPOSE: The efficacy of ophthalmic drug delivery through contact lenses in animal model was explored to evaluate its potential for serving as an alternative to eye drops, which are inefficient vehicles for delivering ophthalmic drugs. METHODS: The efficacy of timolol delivered via contact lenses was compared to eye drops in beagle dogs that suffer from spontaneous glaucoma. Experiments were conducted with NIGHT & DAY™ silicone hydrogel contact lenses and NIGHT & DAY™ loaded with vitamin E, which was included in the lens to extend the release duration of the drug. Timolol was loaded into contact lenses by soaking in drug/phosphate buffered saline solution, and the drug-loaded lenses were subsequently inserted in one of the eyes, with the other eye serving as control. The lenses were replaced every 24 hours, and the pharmacodynamics of intraocular pressure (IOP) and pupil size were monitored in both eyes. RESULTS: The IOP reduction from baseline by NIGHT & DAY™ (5.02 ± 0.83 mmHg) was comparable with that by eye drops with similar drug dosing (4.64 ± 0.41 mmHg). In addition, lenses with one-third of the drug loading as eye drops resulted in the similar IOP reduction, suggesting higher bioavailability for contact lenses compared to eye drops. Inclusion of vitamin E into the lenses did not improve the IOP reduction. The IOP in the untreated eye also decreased from baseline for eye drops (3.17 ± 0.42 mmHg) but it remained relatively unchanged with treatments based on lenses, suggesting reduction in systemic absorption for delivery of drugs by contact lenses. CONCLUSIONS: Ophthalmic drug delivery through contact lenses increases bioavailability and reduces systemic drug uptake.