Timolol, ocular absorption

Hyaluronic acid is a linear polysaccharide found in the highest concentrations in soft connective tissues where it fills an important structural role in the organization of the extracellular matrix (23,24). It has been used in ophthalmic preparations to enhance ocular absorption of timolol, a beta blocker used for the treatment of glaucoma (25), and in a viscoelastic tear formulation for conjunctivitis (26). The covalent binding of adriamycin and daunomycin to sodium hy-aluronate to produce water-soluble conjugates was recently reported (27). 

VHL Lee, S Li, MF Saettone, P Chetoni, H Bundgaard. (1991). Systemic and ocular absorption of timolol prodrugs from erodible inserts. Proc Int Symp Controlled Release Bioact Mater 18 291-292. 

SC Chang, DS Chien, H Bundgaard, VHL Lee. (1988). Relative effectiveness of prodrug and viscous solution approaches in maximizing the ratio of ocular to systemic absorption of topically applied timolol. Exp Eye Res 46 59-69. 

Gasco and co-workers [221] investigated the potential application of o/w lecithin MEs for ocular administration of timolol, in which the drug was present as an ion pair with octanoate. The ocular bioavailability of the timolol ion pair incorporated into the ME was compared to that of an ion pair solution as well as a simple timolol solution. Areas under the curve for the ME and the ion pair solution respectively were 3.5 and 4.2 times higher than that of the simple timolol solution. A prolonged absorption was achieved using the ME with detectable amounts of the drug still present 120 min after instillation. 

KaHa T, Sahninen L, Huupponen R. Systemic absorption of topically applied ocular timolol. J Ocular Pharmacol 1985 1 79-83. 

Early in the development of timolol, some reports indicated the relatively rapid development of tolerance to the drug s ocular hypotensive effects, referred to as escape. The lOP is lower early in the conrse of therapy than with chronic treatment. The lOP resnlts, however, are similar with chronic use of either 0.5% timolol or 0.25% timolol. In addition, the fellow untreated eye may show a decrease in lOP, which most likely resnlts from a consensnal (contralateral) effect. Contralateral effects resnlting from systemic drug absorption can be significant. 

Finne U, Salivirta J, Urtti A. Sodium acetate improves the ocular/ systemic absorption ratio of timolol applied ocularly in monoisopropyl PVM-MA matrices. Int J Pharm 1991 75 Rl—R4. 

Chang, S.-C., and Lee, V. H. L. (J987). Nasal and conjunctival contributions to the systemic absorption of topical timolol in the pigmented rabbit. J. Ocular Pharmacol. 3, 159-16 ). 

Chang, S.C. and Lee, V.H.L.,1987. Nasal and conjuntival contribution to the systemic absoiption of topical timolol in the oigmented rabbit implications in the design of strategies to maximize the ratio of ocular to systemic absorption. J. Ocular Pharmacol. 3 159. 

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